Rituximab-based treatment, HCV replication, and hepatic flares.

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Sagnelli, Evangelista; Pisaturo, Mariantonietta; Sagnelli, Caterina; Coppola, Nicola

2012-01-01

Rituximab, a chimeric mouse-human monoclonal antibody directed to the CD20 antigen expressed on pre-B lymphocytes and mature lymphocytes, causes a profound B-cell depletion. Due to its peculiar characteristics, this drug has been used to treat oncohaematological diseases, B cell-related autoimmune diseases, rheumatoid arthritis, and, more recently, HCV-associated mixed cryoglobulinaemic vasculitis. Rituximab-based treatment, however, may induce an increased replication of several viruses such as hepatitis B virus, cytomegalovirus, varicella-zoster virus, echovirus, and parvovirus B19. Recent data suggest that rituximab-based chemotherapy induces an increase in HCV expression in hepatic cells, which may become a target for a cell-mediated immune reaction after the withdrawal of treatment and the restoration of the immune control. Only a few small studies have investigated the occurrence of HCV reactivation and an associated hepatic flare in patients with oncohaematological diseases receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). These studies suggest that the hepatic flares are frequently asymptomatic, but life-threatening liver failure occurs in nearly 10% of cases.

Rituximab, alkylating agents or combination therapy for gastric mucosa-associated lymphoid tissue lymphoma: a monocentric non-randomised observational study.

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Amiot, A; Lévy, M; Copie-Bergman, C; Dupuis, J; Szablewski, V; Le Baleur, Y; Baia, M; Belhadj, K; Sobhani, I; Leroy, K; Haioun, C; Delchier, J-C

2014-03-01

There is no consensus on the standard treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma for Helicobacter pylori-negative patients and for patients with persistent disease despite H. pylori eradication. To evaluate the comparative efficacy and safety of alkylating agents and rituximab alone or in combination. In this monocentric retrospective study, which included 106 patients who had not been previously treated with anti-cancer agents, we evaluated the efficacy and safety of oral alkylating agents monotherapy (n = 48), rituximab monotherapy (n = 28) and the therapy combining both drugs (n = 30). Evaluations were performed at weeks 6 (W6), 25 (W25), and 52 (W52) and after 2 years (W104). After a median follow-up period of 4.9 years (range 0.4-17.2 years), complete remission and overall response were significantly higher in patients in the combination therapy group at W104 (92% and 100% respectively) compared with patients treated with alkylating agents alone (66% and 68%) and rituximab alone (64% and 73%). The 5-year progression-free survival probabilities were 68%, 70% and 89% in patients treated with alkylating agents alone, rituximab alone and combination therapy respectively. Haematological adverse events were reported in 32 (30%) patients (mostly grade 1) and were more frequent in the two groups receiving alkylating agents (P = 0.05 and P alkylating agents alone. Rituximab has a better safety profile than regimens containing alkylating agents. © 2014 John Wiley & Sons Ltd.

Rapid-infusion rituximab in lymphoma treatment: 2-year experience in a single institution.

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Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

2012-05-01

Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy.

Addition of rituximab to chop does not increase the risk of cardiotoxicity in patients with non-Hodgkin's lymphoma.

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Kilickap, Saadettin; Yavuz, Bunyamin; Aksoy, Sercan; Sahiner, Levent; Dincer, Murat; Harputluoglu, Hakan; Erman, Mustafa; Aytemir, Kudret; Tokgozoglu, Lale; Barista, Ibrahim

2008-01-01

The addition of rituximab to doxorubicin-containing standard chemotherapy significantly improves response to therapy and reduces the risk of death in B-cell non-Hodgkin's lymphoma (NHL) patients. However, the impact of this approach on doxorubicin-induced cardiotoxicity has not been elucidated. Patients who had been planned to receive CHOP or rituximab plus CHOP (R-CHOP) combination chemotherapy with a diagnosis of NHL were included in the study. In all patients, systolic and diastolic parameters were measured by using conventional and pulsed-wave tissue Doppler echocardiography, which is more sensitive than conventional lead-dependent techniques, both before and in the sixth month of therapy. There were 28 (M/F; 14/14) patients on CHOP and 33 (M/F; 16/17) patients on R-CHOP. Median age in CHOP and R-CHOP was 49 and 50 years (P = 0.44), respectively. Cumulative doxorubicin doses were 280 and 286 mg/m(2) on CHOP and R-CHOP (P = 0.65), respectively. None of the patients developed clinically evident congestive heart failure. Parameters of systolic function such as LVEF and FS did not significantly change in any patients. In both arms, tissue Doppler parameters of diastolic function such as lateral E and septal E velocity of mitral annulus decreased significantly after therapy (P 0.05). Conventional Doppler echocardiography yielded consistent findings. Both CHOP and R-CHOP cause diastolic dysfunction in the early period following their administration. The addition of rituximab to CHOP chemotherapy does not significantly increase the risk of doxorubicin-induced cardiotoxicity during this period.

Intralesional rituximab in primary conjunctival follicular lymphoma relapsed.

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Rodríguez Villa, S; Ruiz Rodríguez, M J; Vargas Pabón, M

2017-07-01

A 49-year-old woman experienced a local relapse of a primary follicular lymphoma (FL) of the conjunctiva. She received 4 weekly intra-lesional injections followed by 6 monthly injections of rituximab (6mg/ml). A clinical response was achieved after first injection. No adverse ocular event or signs of lymphoma relapse were seen after 10 months of follow-up. Intralesional administration of rituximab for treating primary FL of the conjunctiva was an effective and safe therapeutic option; therefore it could be an alternative to other conventional treatments, such as radiotherapy or chemotherapy. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Rapid-Infusion Rituximab in Lymphoma Treatment: 2-Year Experience in a Single Institution

Science.gov (United States)

Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

2012-01-01

Purpose: Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Patients and Methods: Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. Results: From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. Conclusion: A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy. PMID:22942806

Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

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Khor, Sara; Beca, Jaclyn; Krahn, Murray; Hodgson, David; Lee, Linda; Crump, Michael; Bremner, Karen E; Luo, Jin; Mamdani, Muhammad; Bell, Chaim M; Sawka, Carol; Gavura, Scott; Sullivan, Terrence; Trudeau, Maureen; Peacock, Stuart; Hoch, Jeffrey S

2014-08-12

Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice. We performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG). Rituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and $110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age. Our results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was

Rituximab is associated with improved survival in Burkitt lymphoma: a retrospective analysis from two US academic medical centers.

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Wildes, Tanya M; Farrington, Laura; Yeung, Cecilia; Harrington, Alexandra M; Foyil, Kelley V; Liu, Jingxia; Kreisel, Friederike; Bartlett, Nancy L; Fenske, Timothy S

2014-02-01

Burkitt lymphoma (BL) is a rare, highly aggressive B-cell malignancy treated most successfully with brief-duration, high-intensity chemotherapeutic regimens. The benefit of the addition of rituximab to these regimens remains uncertain. We sought to examine the effectiveness of chemotherapy with and without rituximab in patients with BL. This study is a retrospective cohort study of all adult patients with BL diagnosed and treated with modern, dose-intense chemotherapeutic regimens from 1998-2008 at two tertiary care institutions. All cases were confirmed by application of WHO 2008 criteria by hematopathologists. Medical records were reviewed for patient-, disease-, and treatment- related factors as well as treatment response and survival. Factors associated with survival were analyzed using Cox proportional hazards modeling. A total of 35 patients were analyzed: 18 patients received rituximab with chemotherapy (R-chemo) and 17 received chemotherapy (chemo) alone. The median age was 42 (range 20-74 years); 57% were male; 71% had Ann Arbor Stage IV disease; 33% had central nervous system involvement; 78% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. R-chemo was associated with significantly longer overall survival (OS) than chemo alone (5-year OS 70% and 29%, respectively, p = 0.040). On multivariate regression analysis, poor performance status and central nervous system involvement were associated with poorer survival. The addition of rituximab to chemotherapy was associated with improved OS in patients with Burkitt lymphoma. Poor performance status and central nervous system involvement were prognostically significant on multivariate analysis.

The Role of Rituximab in Lymphomas O papel do Rituximab nos linfomas

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Bertrand Coiffier

2002-01-01

Full Text Available Over the last years the treatment of non-Hodgkin's lymphoma underwent a great advance in relation to the diagnosis, classification, high-dose chemotherapy, and hematopoietic stem cell transplantation. Simultaneously with this, there was the development of new drugs and support therapy which enabled an improvement in the evolution and survival of the patients. The use of monoclonal antibodies against cancer cells is an old idea and in this report the results of the role of the anti-CD20-Rituximab in lymphomas is discussed.Nos últimos anos o tratamento do linfomas não Hodgkin apresentou um grande avanço no diagnóstico, classificação, quimioterapia com altas doses e o transplante de células percursoras hematopoiéticas. Simultaneamente houve o desenvolvimento de novas drogas e no tratamento de suporte o que possibilita um avanço na evolução e sobrevida dos pacientes. A idéia do emprego de anticorpos monoclonais no tratamento do câncer é antiga e neste relato são apresentados os resultados e o papel do anti-CD20-Rituximab nos linfomas.

Combined radiotherapy-chemotherapy

International Nuclear Information System (INIS)

Steel, G.G.

1989-01-01

This paper presents the clinically confirmed benefits of combined chemotherapy-radiotherapy. They have been found in a small group of diseases that respond to chemotherapy alone. According to the author, only when a drug or drug combination has the ability to eradicate occult disease or substantially to reduce the size of objectively measurable disease is there likely to be an demonstrable benefit from its use in conjunction with radiotherapy. It is the author's belief that the immediate future lies in selecting drugs and patients in which a good chemotherapeutic response can be expected, avoiding drugs that seriously enhance radiation damage to normal tissues and keeping drug and radiation treatments far enough apart in time to minimize interactions

Chemotherapy in combined and multimodality treatment

International Nuclear Information System (INIS)

Anon.

1989-01-01

It is shown that chemotherapy of tumors of various localizations developes intensively in the last few years. It is connected with discovery and adoption of new active antitumoral preparations, such as alkylating preparations, antimetabolites, antitumoral antibiotics, hormonal preparations. To create the rational effective conditions of chemotherapy a study was made on kinetics of tumor gowth, molecular mechanisms of interaction of cytostatics and cells of malignant tumor. Main factors of chemotherapy combination with radiotherapy when treating numerous malignant tumors were considered. Effectiveness of using chemotherapy in combination with other methods of treatment was shown

Combination Chemotherapy for Influenza

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Robert G. Webster

2010-07-01

Full Text Available The emergence of pandemic H1N1 influenza viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses underscore the urgency of novel approaches to chemotherapy for human influenza infection. Anti-influenza drugs are currently limited to the neuraminidase inhibitors (oseltamivir and zanamivir and to M2 ion channel blockers (amantadine and rimantadine, although resistance to the latter class develops rapidly. Potential targets for the development of new anti-influenza agents include the viral polymerase (and endonuclease, the hemagglutinin, and the non-structural protein NS1. The limitations of monotherapy and the emergence of drug-resistant variants make combination chemotherapy the logical therapeutic option. Here we review the experimental data on combination chemotherapy with currently available agents and the development of new agents and therapy targets.

Feasibility and toxicity of concomitant radio/immunotherapy with MabThera (Rituximab {sup registered}) for patients with non-Hodgkin's lymphoma. Results of a prospective phase I/II study

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Haidenberger, Alfred; Popper, Bela-Andre; Skvortsova, Ira; Lukas, Peter [Medical Univ. Innsbruck (Austria). Dept. of Radiotherapy/Radiooncology; Fromm-Haidenberger, Sabine [Hospital Gmunden (Austria). Inst. of Radiology; Vries, Alexander de [Hospital Feldkirch (Austria). Dept. of Radiotherapy/Radiooncology; Steurer, Michael; Kantner, Johanna; Gunsilius, Eberhard [Medical Univ. Innsbruck (Austria). Dept. of Hematology

2011-05-15

Purpose: Non-Hodgkin's lymphomas (NHL) have a high radio- and chemosensitivity. Although initially responsive, approximately 50% of low grade B-cell lymphomas relapse after 10-15 years. Besides chemo- and radiotherapy, rituximab, a mouse/human chimeric antibody targeting CD20 antigen on the surface of B-cell lymphoma cells, is another treatment approach. In vitro data showed potentiation of radiation-induced apoptosis by addition of rituximab. The purpose of this study was to evaluate the feasibility and toxicity of radiotherapy with concomitant application of rituximab in NHL patients. Patients and Methods: A total of 21 patients with B-cell lymphoma (stage I: n = 11; II: n = 5; III: n = 1; IV: n = 4) were included in this study, treated with radiotherapy of 30-40 Gy and weekly application of rituximab (375 mg/m{sup 2}). Nine patients had R-CHOP chemotherapy previously, 1 patient leuceran chemotherapy, and 2 patients an initial treatment with 6 cycles of rituximab. Mean time of follow-up was 41.7 months. Results: No grade 4 toxicity or treatment-related death was observed. In 1 patient, rituximab application had to be stopped after 3 cycles due to radiation-induced side effects. No late toxicities were reported. All patients were in complete remission after treatment. Progression or relapse was observed in 6 patients (28%); the mean time to progression was 27 months. The mean overall survival (OS) was 53 months. Conclusion: Combined radio/immunotherapy is feasible and safe. Treatment was well tolerated, no late toxicities were observed, and treatment outcome is promising. Randomized trials are necessary to clarify the benefit of this treatment approach and its applicability. (orig.)

Critical appraisal of rituximab in the maintenance treatment of advanced follicular lymphoma

Directory of Open Access Journals (Sweden)

Aguiar-Bujanda D

2015-10-01

Full Text Available David Aguiar-Bujanda, María Jesús Blanco-Sánchez, María Hernández-Sosa, Saray Galván-Ruíz, Samuel Hernández-Sarmiento Department of Medical Oncology, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain Abstract: Rituximab is an IgG1, chimeric monoclonal antibody specifically designed to recognize the CD20 antigen expressed on the surface of normal and malignant B-lymphocytes, from the B-cell precursor to the mature B-cells of the germinal center, and by most neoplasms derived from B-cells. After 2 decades of use, rituximab is firmly positioned in the treatment of follicular lymphoma (FL, both in the front line and in the relapsing disease, improving previous results by including it in classical chemotherapy regimens. However, the pharmacology of rituximab continues to generate controversial issues especially regarding the mechanisms of action in vivo. The contribution of rituximab as a maintenance treatment in FL has been significant progress in the management of this disease without an increase in side effects or a decrease in the quality of life of patients. With the widespread use of rituximab, there are new security alerts and side effects not previously detected in the pivotal trials that clinicians should learn to recognize and manage. In this article, we will review the pharmacokinetics and pharmacodynamics of rituximab, the management issues in the treatment of advanced FL focusing on maintenance rituximab, its long-term efficacy and safety profile, and its effect on the quality of life. Keywords: follicular lymphoma, long-term efficacy, maintenance, rituximab, toxicity

Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis C.

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Dizdar, Omer; Tapan, Umit; Aksoy, Sercan; Harputluoglu, Hakan; Kilickap, Saadettin; Barista, Ibrahim

2008-05-01

Reactivation of hepatitis B virus (HBV) infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented complication. However, data on the consequence of chemotherapy on the course of hepatitis C virus (HCV) infection in HCV+ patients have been controversial. Here, we review the current knowledge about the complications related to HCV in lymphoma patients receiving chemotherapy/immunosuppressive therapy. Although less frequent than HBV, these complications occur in a subset of patients with mortality rates up to 45%. Therefore, baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High-risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co-infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels.

Combined chemotherapy including platinum derivatives for medulloblastoma. The usefulness as maintenance chemotherapy

International Nuclear Information System (INIS)

Sasaki, Hikaru; Otani, Mitsuhiro; Yoshida, Kazunari; Kagami, Hiroshi; Shimazaki, Kenji; Toya, Shigeo; Kawase, Takeshi

1997-01-01

The authors reviewed 24 cerebellar medulloblastoma patients treated at Keio University to determine usefulness of combined chemotherapy including platinum derivatives (cisplatin, carboplatin) as the induction and maintenance treatment. All patients underwent radical surgery and craniospinal irradiation. Ten received adjuvant chemotherapy other than platinum derivatives (mainly with nitrosourea compounds), five were treated by induction and maintenance chemotherapy including platinum derivatives, and nine patients did not undergo chemotherapy. The progression-free survival rate of patients treated with platinum derivatives was better than that of patients treated with other modes of chemotherapy and also that of patients who did not receive chemotherapy. The results were especially good in the case of four patients treated with maintenance chemotherapy consisting of carboplatin and etoposide, two of whom had been free from relapse beyond the risk period of Collins. The occurrences of toxicity in maintenance chemotherapy with carboplatin and etoposide were limited to transient leucopenia. The present study indicates combined chemotherapy including platinum derivatives benefits patients with medulloblastoma, and could be useful, especially as maintenance treatment. (author)

Lymphomatoid granulomatosis of central nervous system and lung driven by epstein barr virus proliferation: successful treatment with rituximab-containing chemotherapy.

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Fernandez-Alvarez, Ruben; Gonzalez, Me; Fernandez, Almudena; Gonzalez-Rodriguez, Ap; Sancho, Jm; Dominguez, Francisco; Fernandez, Carmen

2014-01-01

Lymphomatoid granulomatosis (LYG) is a very rare Epstein-Barr virus (EBV) associated B-cell lymphoproliferative disorder. We report the case of a 41-year-old man who presented with fever and respiratory symptoms. Computed tomography showed multiple nodules in both lung fields. Polymerase chain reaction (PCR) analysis for EBV was positive in bronchoalveolar lavage and biopsy of lung node yielded a diagnosis of LYG, grade III. Shortly after initiation of treatment with agressive chemotherapy, neurological deterioration appeared. Neuroimaging findings revealed hydrocephalus and PCR analysis of the cerebrospinal fluid (CSF) was positive for EBV. Treatment with intravenous rituximab led to rapid reduction of EBV load in CSF, along with clinical and radiological improvement. After completion of treatment with immunochemotherapy, an autologous stem cell transplantation was performed. Patient stays in remission 18 months after diagnosis.

Combination radiotherapy and chemotherapy for primary lung cancer

International Nuclear Information System (INIS)

Nishikawa, Kiyoshi; Koga, Kenji; Kusuhara, Toshiyuki; Kodama, Takao; Takeuchi, Midori; Watanabe, Katsushi

1984-01-01

Fifty-six patients with carcinoma of the lung treated with radiotherapy alone or combination of chemotherapy were reviewed. Radiation was given with a 10MV photon beam by a linear accelerator. A fraction dose of 2Gy (200 rad) was given routinely 5 times a week. Combined durgs consist of 5FU or FT-207 in monochemotherapy and METT, MFC, or METVFC in combination chemotherapy. 5 year survival rate of all patients was 3.8%. As for the stage classification, 5 year survival rate is 30% in Stage I and II cancer, but there was no 3 year survivor in Stage III cancer and 2 year survivor in Stage IV cancer. As for the cell types, cases of adenocarcinoma had worse prognosis than them of squamous cell carcinoma and small cell carcinoma. The prognosis of patients treated with combination of radiotherapy and chemotherapy was similar to that of patients treated with radiotherapy alone. These results suggest that combined chemotherapy did not influence tumor control. Some discussion on the treatment modality of chemotherapy are made, emphasizing untoward effect of chemotherapy on immunopotency. (author)

Experimental study on combination of chemotherapy and radiotherapy

International Nuclear Information System (INIS)

Tanaka, Juichi

1986-01-01

Recently, by applying multidrug therapy using cisplatin and bleomycin to the treatment of head and neck cancer, the response rate of chemotherapy has been markedly increased and thus, chemotherapy has taken an important part in the treatment of head and neck cancer. In this paper a clinical application of chemotherapy in combination with radiotherapy was evaluated from the point of the cure rate and also preservation of the structures and the functions of the head and neck region. In order to test the advantage or usefulness of initial chemotherapy followed by radiotherapy (= pre-radiation chemotherapy), the experimental study on combination of chemotherapy and radiotherapy was designed by using ICR mice and Ehrlich solid carcinoma. Cisplatin and peplomycin, a newly developed derivative of bleomycin, were used as chemotherapeutic agents. Tumor growth delay rate was chosen as a parameter to indicate the effectiveness. Results obtained are as follows. 1. Combination chemotherapy of cisplatin and peplomycin was more effective than each single agent on Ehrlich solid carcinoma. Synergistic effect was obtained by higher dose. So, the combination of cisplatin and peplomycin was proved to be eligible for pre-radiation chemotherapy. 2. Synergistic effect of chemotherapy and radiotherapy was observed when chemotherapy was used prior to radiotherapy on Ehrlich solid carcinoma. 3. Even their additional effect was not recognized when radiotherapy preceded to chemotherapy on Ehrlich solid carcinoma. 4. No severe toxic effect was seen in the mice. The experimental results made it clear that pre-radiation chemotherapy is beneficial to the treatment of head and neck cancer. (author)

Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide in rituximab-treated rheumatoid arthritis patients

DEFF Research Database (Denmark)

Chatzidionysiou, Katerina; Lie, Elisabeth; Nasonov, Evgeny

2012-01-01

is an effective and safe alternative to methotrexate as concomitant treatment with rituximab. Slightly better results were obtained by the combination of rituximab and leflunomide than rituximab and methotrexate, raising the possibility of a synergistic effect of leflunomide and rituximab.......OBJECTIVES: To compare the effectiveness and safety of rituximab alone or in combination with either methotrexate or leflunomide.METHODS: 10 European registries submitted anonymised datasets with baseline, 3, 6, 9 and 12-month clinical data from patients who started rituximab.RESULTS: 1195 patients...

Radiotherapy of esophageal cancer in combination with chemotherapy

International Nuclear Information System (INIS)

Jinnouchi, Shoshi; Koga, Kenji; Nishikawa, Kiyoshi; Kihara, Yasushi; Kusuhara, Toshiyuki; Watanabe, Katuji

1983-01-01

The significance of combination of chemotherapy in radiotherapy for esophageal cancer was evaluated in 32 patients. They were irradiated routinely in 5 times a weeks with a fraction dose of 200 rad by 10MV-X-ray linear accelerator. Combined drugs consist of Bleomycin or Pepleomycin in two-third and 5FU or FT-207 in one-third. There was statistically no significance between the results of radiation alone and combined chemotherapy, and the improvement of survival rate could not be obtained by combining chemotherapy. Some discussion on the causes of this unimprovement were made. (author)

Combined radiotherapy and chemotherapy for head and neck cancer

International Nuclear Information System (INIS)

Inuyama, Yukio; Fujii, Masato; Tanaka, Juichi; Takaoka, Tetsuro; Hosoda, Hyonosuke; Kawaura, Mitsuhiro; Toji, Masao

1988-01-01

There are 4 modalities of combined radiotherapy and chemotherapy which include (1) concurrent radiotherapy and chemotherapy, (2) sequential use of radiotherapy and chemotherapy (pre-radiation chemotherapy), (3) pre-radiation chemotherapy followed by concurrent radiation and chemotherapy, and (4) alternating use of radiotherapy and chemotherapy based upon Looney's hypothesis. We studied concurrent use of radiotherapy and UFT by means of animal experimentation and clinical trials. The results obtained revealed that UFT was a most suitable agent together with 5-fluorouracil for concurrent application of radiotherapy and chemotherapy. Neo-adjuvant chemotherapy including pre-radiation chemotherapy was also studied in cases of maxillary sinus carcinoma and nasopharyngeal carcinoma. From the results, it seemed desirable to use cisplatin and bleomycin analogs sequentially in combined chemotherapy and radiotherapy. Neo-adjuvant chemotherapy should be studied successively to improve local tumor control rates and prevent distant metastases. For future perspectives, new trials of alternating radiotherapy and chemotherapy based upon Looney's hypothesis seem necessary. (author)

Preparation & in vitro evaluation of 90Y-DOTA-rituximab

Science.gov (United States)

Kameswaran, Mythili; Pandey, Usha; Dash, Ashutosh; Samuel, Grace; Venkatesh, Meera

2016-01-01

Background & objectives: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin's lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with 90Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. Methods: Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. Results: Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with 90Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with 90Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant Kd for 90Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of 90Y-DOTA-rituximab. Interpretation & conclusions: p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90Y was carried out. In vitro studies carried

Targeting chemotherapy-resistant leukemia by combining DNT cellular therapy with conventional chemotherapy.

Science.gov (United States)

Chen, Branson; Lee, Jong Bok; Kang, Hyeonjeong; Minden, Mark D; Zhang, Li

2018-04-24

While conventional chemotherapy is effective at eliminating the bulk of leukemic cells, chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that hinders conventional therapies and contributes to disease relapse, and ultimately patient death. We have recently shown that allogeneic double negative T cells (DNTs) are able to target the majority of primary AML blasts in vitro and in patient-derived xenograft models. However, some primary AML blast samples are resistant to DNT cell therapy. Given the differences in the modes of action of DNTs and chemotherapy, we hypothesize that DNT therapy can be used in combination with conventional chemotherapy to further improve their anti-leukemic effects and to target chemotherapy-resistant disease. Drug titration assays and flow-based cytotoxicity assays using ex vivo expanded allogeneic DNTs were performed on multiple AML cell lines to identify therapy-resistance. Primary AML samples were also tested to validate our in vitro findings. Further, a xenograft model was employed to demonstrate the feasibility of combining conventional chemotherapy and adoptive DNT therapy to target therapy-resistant AML. Lastly, blocking assays with neutralizing antibodies were employed to determine the mechanism by which chemotherapy increases the susceptibility of AML to DNT-mediated cytotoxicity. Here, we demonstrate that KG1a, a stem-like AML cell line that is resistant to DNTs and chemotherapy, and chemotherapy-resistant primary AML samples both became more susceptible to DNT-mediated cytotoxicity in vitro following pre-treatment with daunorubicin. Moreover, chemotherapy treatment followed by adoptive DNT cell therapy significantly decreased bone marrow engraftment of KG1a in a xenograft model. Mechanistically, daunorubicin increased the expression of NKG2D and DNAM-1 ligands on KG1a; blocking of these pathways attenuated DNT-mediated cytotoxicity. Our results demonstrate the feasibility and benefit of using DNTs as

Enhanced efficacy of gemcitabine in combination with anti-CD20 monoclonal antibody against CD20+ non-Hodgkin's lymphoma cell lines in vitro and in scid mice

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Jin Fang

2005-08-01

Full Text Available Abstract Background Despite exciting new targeted therapeutics against non-Hodgkin's lymphoma (NHL, chemotherapy remains a cornerstone of therapy. While purine nucleoside analogs have significant activity in low grade NHL, the pyrimidine nucleoside analog gemcitabine has been less extensively studied, but has important activity. Use of the anti-CD20 monoclonal antibody rituximab in combination with chemotherapy for B-NHL is becoming prevalent in clinical practice, but has not been extensively studied in pre-clinical models. Methods We have tested the activity of gemcitabine ± rituximab in vitro and in scid/human NHL xenograft models. We used two t(14;18+, CD20+ follicular B cell NHL cell lines, DoHH2 a transformed NHL line and WSU-FSCCL isolated from pleural fluid of a patient with indolent NHL. Results Gemcitabine is cytotoxic to DoHH2 and WSU-FSCCL cells in vitro, and the IC50 is 2–3 fold lower in the presence of rituximab. Apoptosis is also enhanced in the presence of rituximab. Clearance of NHL cells from ascites in scid mice is prolonged by the combination, as compared with either agent alone. Most importantly, survival of scid mice bearing human NHL cells is significantly prolonged by the combination of gemcitabine + rituximab. Conclusion Based on our pre-clinical data showing prolonged survival of mice bearing human lymphoma cell line xenografts after treatment with gemcitabine + anti-CD20 antibody, this combination, expected to have non-overlapping toxicity profiles, should be explored in clinical trials.

Radioimmunotherapy using 131I-rituximab in patients with advanced stage B-cell non-Hodgkin's lymphoma: initial experience

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Bienert, Maren; Reisinger, Ingrid; Humplik, Beatrice I.; Reim, Christel; Kroessin, Thomas; Avril, Norbert; Munz, Dieter L.; Srock, Stefanie; Pezzutto, Antonio

2005-01-01

The aim of this study was to evaluate the safety, toxicity and therapeutic response of non-myeloablative radioimmunotherapy using 131 I-rituximab in previously heavily treated patients with B-cell non-Hodgkin's lymphoma (B-NHL). Nine patients with relapsed, refractory or transformed B-NHL received ten radioimmunotherapies. Patients had a median of 5 (range 2-7) prior standard therapies. Four patients had received prior high-dose chemotherapy followed by autologous stem cell transplantation, and eight had received prior rituximab therapy. Histopathology consisted of four mantle cell, one follicular and four diffuse large B-cell lymphomas. Rituximab, a monoclonal chimeric anti-CD20 antibody (IDEC-C2B8), was labelled with 131 I using the Iodogen method. The administered activity (2,200±600 MBq) was based on a dosimetrically calculated 45 cGy total-body radiation dose. All patients received an infusion of 2.5 mg/kg of rituximab prior to administration of the radiopharmaceutical. No acute adverse effects were observed after the administration of 131 I-rituximab. Radioimmunotherapy was safe in our patient group and achieved one complete response ongoing at 14 months and two partial responses progressing at 12 and 13 months after treatment. One partial responder was re-treated with radioimmunotherapy and achieved an additional progression-free interval of 7 months. Four non-responders with bulky disease died 4.8±2.0 months after therapy. Three patients had an elevated serum lactate dehydrogenase (LDH) level prior to radioimmunotherapy and none of the patients responded. Of two patients who received radioimmunotherapy as an additional treatment after salvage chemotherapy, one continues to be disease-free at 9 months and one relapsed at 5 months' follow-up. Reversible grade 3 or 4 haematological toxicity occurred in seven of nine patients. Median nadirs were 35 days for platelets, 44 days for leucocytes and 57 days for erythrocytes. (orig.)

Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

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Jegadeesh, Naresh; Rajpara, Raj; Esiashvili, Natia; Shi, Zheng [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Liu, Yuan [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia (United States); Okwan-Duodu, Derrick [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Flowers, Christopher R. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Medical Oncology, Emory University, Atlanta, Georgia (United States); Khan, Mohammad K., E-mail: drkhurram2000@gmail.com [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

2015-05-01

Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy.

Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

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Jegadeesh, Naresh; Rajpara, Raj; Esiashvili, Natia; Shi, Zheng; Liu, Yuan; Okwan-Duodu, Derrick; Flowers, Christopher R.; Khan, Mohammad K.

2015-01-01

Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy

A salvage chemotherapy of R-P-IMVP16/CBDCA consisting of rituximab, methylprednisolone, ifosfamide, methotrexate, etoposide, and carboplatin for patients with diffuse large B cell lymphoma who had previously received R-CHOP therapy as first-line chemotherapy.

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Matsumoto, Takuro; Hara, Takeshi; Shibata, Yuhei; Nakamura, Nobuhiko; Nakamura, Hiroshi; Ninomiya, Soranobu; Kitagawa, Junichi; Kanemura, Nobuhiro; Goto, Naoe; Kito, Yusuke; Kasahara, Senji; Yamada, Toshiki; Sawada, Michio; Miyazaki, Tatsuhiko; Takami, Tsuyoshi; Takeuchi, Tamotsu; Moriwaki, Hisataka; Tsurumi, Hisashi

2017-09-01

We have reported the efficacy of the salvage chemotherapy P-IMVP16/CBDCA for patients with diffuse large B cell lymphoma (DLBCL) who had previously received CHOP before the availability of rituximab (R). Here, we confirmed the efficacy of R combined with P-IMVP16/CBDCA as a salvage chemotherapy for patients with DLBCL, who had previously received R-CHOP. We retrospectively analysed 59 patients with relapse or refractory DLBCL (38 male patients and 21 female patients) presenting between June 2004 and June 2013. The patients received R 375 mg/m 2 on day 1, methylprednisolone 1000 mg/body for 3 days (from day 3 to day 5), ifosfamide 1000 mg/m 2 for 5 days (from day 3 to day 7), methotrexate 30 mg/m 2 on day 5 and day 12, etoposide 80 mg/m 2 for 3 days (from day 3 to day 5), and carboplatin 300 mg/m 2 on day 3 every 21 days. Patients aged 70 years or older were given 75% of the standard dose. The overall response rate (complete response + partial response) was 64.4%. The 2-year overall survival rate was 55.3%. The 2-year progression free survival rate was 34.7%. The 2-year overall survival rate was 61.5% for the relapse patients, and 15.6% for the refractory patients (p effects were mild and tolerable. The R-P-IMVP-16/CBDCA regimen displayed a significant activity in relapsed DLBCL, with acceptable toxicity, and should be considered a candidate for salvage chemotherapy. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Time Savings with Rituximab Subcutaneous Injection versus Rituximab Intravenous Infusion: A Time and Motion Study in Eight Countries

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De Cock, Erwin; Kritikou, Persefoni; Sandoval, Mariana; Tao, Sunning; Wiesner, Christof; Carella, Angelo Michele; Ngoh, Charles; Waterboer, Tim

2016-01-01

Background Rituximab is a standard treatment for non-Hodgkin lymphoma. The SABRINA trial (NCT01200758) showed that a subcutaneous (SC) rituximab formulation did not compromise efficacy or safety compared with intravenous (IV) infusion. We aimed to quantify active healthcare professional (HCP) time and patient chair time for rituximab SC and IV, including potential time savings. Methods This non-interventional time and motion study was run in eight countries and 30 day oncology units. Rituximab SC data were collected alongside the MabCute trial (NCT01461928); IV data were collected per routine real-world practice. Trained observers recorded active HCP time for pre-specified tasks (stopwatch) and chair time (time of day). A random intercept model was used to analyze active HCP time (by task and for all tasks combined) in the treatment room and drug preparation area, drug administration duration, chair time and patient treatment room time by country and/or across countries. Active HCP and chair time were extrapolated to a patient’s first year of treatment (11 rituximab sessions). Results Mean active HCP time was 35.0 and 23.7 minutes for IV and SC process, respectively (-32%, p time was 27–58%. Absolute reduction in extrapolated active HCP time (first year of treatment) was 1.1–5.2 hours. Mean chair time was 262.1 minutes for IV, including 180.9 minutes infusion duration, vs. 67.3 minutes for SC, including 8.3 minutes SC injection administration (-74%, p time for the first year of treatment was 3.1–5.5 eight-hour days. Conclusions Compared with rituximab IV, rituximab SC was associated with reduced chair time and active HCP time. The latter could be invested in other activities, whereas the former may lead to more available appointments, reducing waiting lists and increasing the efficiency of day oncology units. Trial Registration ClinicalTrials.gov NCT01200758 PMID:27362533

Preparation & in vitro evaluation of ⁹⁰Y-DOTA-rituximab.

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Kameswaran, Mythili; Pandey, Usha; Dash, Ashutosh; Samuel, Grace; Venkatesh, Meera

2016-01-01

Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin's lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with [90] Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90 Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with [90] Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90 Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with [90] Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant K d for 90 Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of [90] Y-DOTA-rituximab. p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90 Y was carried out. In vitro studies carried out in Raji cells showed the specificity of the

Tolerance of radiotherapy combined with adjuvant chemotherapy in breast cancer

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Hrafnkelsson, J.; Nilsson, K.; Soederberg, M.

1987-01-01

Forty-three postmenopausal breast cancer patients with axillary lymph node metastasis were randomized to receive postoperative radiotherapy (45 Gy) or the combination of radiotherapy and 6 months of chemotherapy. Forty-three premenopausal patients had postoperative radiotherapy and were randomized to receive one of two different chemotherapy combinations. Pulmonary fibrosis was roentgenologically registered in approximately 70% of the total patient population six months after initiation of therapy. Addition of chemotherapy with doxorubicin and cyclophosphamide significantly increased the proportion of patients with pulmonary fibrosis compared with patients treated with radiotherapy only or radiotherapy combined with cyclophosphamide, methotrexate and 5-fluorouracil. Premenopausal patients tolerated the combination of radiotherapy and chemotherapy better than postmenopausal patients of whom approximately 30% did not tolerate 65% or more of prescribed total dose of chemotherapy. (orig.)

Malignant lymphoma of the vagina successfully treated with rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone.

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Nasu, K; Okamoto, M; Nishida, M; Takai, N; Narahara, H

2012-01-01

Primary malignant lymphoma of the vagina is extremely rare. The most common histologic subtype is diffuse large B-cell lymphoma (DLBCL). We report a case of vaginal DLBCL successfully treated with chemotherapy consisting of rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone (R-CHOP), followed by pelvic irradiation. A 44-year-old Japanese woman was admitted complaining of atypical genital bleeding and puruloid vaginal discharge. Gynecological examination showed an ulceration of the vaginal wall and a hard mass the size of a goose egg beneath the left vaginal wall, which had infiltrated to the left pelvic wall. The pathological diagnosis based on a punch biopsy taken from the vaginal tumor was non-Hodgkin's lymphoma. Based on immunohistochemical study, the tumor was subclassified as activated B-cell type DLBCL. The patient was diagnosed with Ann Arbor Stage IEA DLBCL and Stage III vaginal cancer, according to the International Federation of Gynecologists and Obstetricians (FIGO) classification system. She was successfully treated by six courses of R-CHOP, followed by radiation therapy. The patient is well without evidence of disease 13 months following the initial treatment. Little attention has been paid to the use of rituximab in addition to conventional chemotherapy and the importance of clinical and morphological subgrouping of DLBCL arising in the vagina. The present case indicates that the effects of rituximab on the prognosis of vaginal DLBCL must be evaluated, and that clinical use of immunophenotypic subgrouping should be considered for vaginal DLBCL.

EXPERIENCE OF TREATMENT WITH RITUXIMAB IN PATIENT WITH JUVENILE POLYARTERITIS

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E.I. Alexeeva

2011-01-01

Full Text Available The article presents a case report of severe course of nodular polyarteritis. The disease was highly active, aggressive, and refractory to treatment with corticosteroids and cyclophosphamide combined with plasmapheresis and drugs for microcirculation improvement. The treatment with chimerical anti-CD20 monoclonal antibodies — rituximab — was successful. Symptoms of intoxication and tromboangiatic syndrome decreased in 4 weeks. Disease was stopped up to 16th week. The case report demonstrates high efficacy of rituximab: patient with severe nodular polyarteritis remains clinical and laboratory remission during 52 weeks.Key words: children, nodular polyarteritis, rituximab.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (2: 193–200

Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

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Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others

2005-01-01

Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20∼70 mg) immediately prior to administration of therapeutic dose (51.4∼152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted

Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

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Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others [Korea University Medical School, Seoul (Korea, Republic of)

2005-07-01

Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20{approx}70 mg) immediately prior to administration of therapeutic dose (51.4{approx}152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted.

Impact of obinutuzumab alone and in combination for follicular lymphoma

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Sarraf Yazdy M

2017-10-01

Full Text Available Maryam Sarraf Yazdy, Bruce D Cheson Division of Hematology-Oncology, Georgetown University Hospital, Lombardi Comprehensive Cancer Center, Washington, DC, USA Abstract: Although rituximab-based chemoimmunotherapy prolongs the survival of patients with follicular lymphoma (FL, this disease is considered incurable in most patients. Thus, new therapies are needed not only for those in the relapsed/refractory setting, but also for initial treatment. Obinutuzumab (G, GA101 is a third-generation, fully humanized type II glycoengineered, anti-CD20 monoclonal antibody that results in increased direct cell death and antibody-dependent, cell-mediated cytotoxicity/phagocytosis compared to rituximab. Obinutuzumab has significant antitumor activity when used alone or in combinations in untreated or relapsed refractory FL patients. Studies have demonstrated its ability to prolong progression-free survival and, in some cases, overall survival, and to eliminate minimal residual disease. Several ongoing trials are investigating combinations with chemotherapy, immunomodulators, targeted drugs, and immunotherapy agents. G is generally well tolerated, with associated adverse effects including infusion-related reactions, neutropenia, thrombocytopenia, and reactivation of hepatitis B virus. Future studies with this antibody should focus on identifying predictive markers and developing chemotherapy-free combinations that will improve the outcome of patients with FL. Keywords: obinutuzumab, follicular lymphoma, MRD, monoclonal antibody

Rituximab treatment for fibrillary glomerulonephritis.

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Hogan, Jonathan; Restivo, Michaela; Canetta, Pietro A; Herlitz, Leal C; Radhakrishnan, Jai; Appel, Gerald B; Bomback, Andrew S

2014-10-01

Approximately 50% of patients with fibrillary glomerulonephritis (GN) progress to end-stage renal disease (ESRD) within 2 years of diagnosis, and no standard therapy exists. The data on rituximab therapy for fibrillary GN are limited and have inconsistent outcomes. Here, we report the largest case series to date using rituximab for fibrillary GN. Retrospective chart reviews were conducted on 12 patients with fibrillary GN who were treated with rituximab (1 g i.v. × 2 doses or 375 mg/m(2) × 4 doses) at the Center for Glomerular Diseases at Columbia University Medical Center. Non-progression of disease was defined as stable/improved serum creatinine (SCr) with a minimum of 1 year of follow-up. The median SCr was 2.1 (range 0.7-2.7) mg/dL, median estimated glomerular filtration rate (eGFR) 39 (range 21-98) mL/min/1.73 m(2) and median proteinuria 4497 (range 210-7542) mg/day at the time of rituximab initiation. Four patients had received immunosuppression before rituximab, and nine received immunosuppression after rituximab, with four receiving a second rituximab course. Four of 12 patients were non-progressors, 3 of 12 had progressive renal dysfunction without reaching ESRD, and 5 patients reached ESRD. The median follow-up for patients who did not reach ESRD was 38 (range 14-76) months after rituximab treatment. Non-progressors had lower SCr values, higher eGFRs and shorter median duration from diagnosis to treatment than progressors. No serious adverse events were noted. Rituximab therapy was associated with non-progression of renal disease in 4 of 12 patients. At the time of treatment, these non-progressors had better renal function and shorter time from diagnosis to treatment than progressors. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Rituximab selectively suppresses specific islet antibodies.

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Yu, Liping; Herold, Kevan; Krause-Steinrauf, Heidi; McGee, Paula L; Bundy, Brian; Pugliese, Alberto; Krischer, Jeff; Eisenbarth, George S

2011-10-01

The TrialNet Study Group evaluated rituximab, a B-cell-depleting monoclonal antibody, for its effect in new-onset patients with type 1A diabetes. Rituximab decreased the loss of C-peptide over the first year of follow-up and markedly depleted B lymphocytes for 6 months after administration. This article analyzes the specific effect of rituximab on multiple islet autoantibodies. A total of 87 patients between the ages of 8 and 40 years received either rituximab or a placebo infusion weekly for four doses close to the onset of diabetes. Autoantibodies to insulin (IAAs), GAD65 (GADAs), insulinoma-associated protein 2 (IA2As), and ZnT8 (ZnT8As) were measured with radioimmunoassays. The primary outcome for this autoantibody analysis was the mean level of autoantibodies during follow-up. Rituximab markedly suppressed IAAs compared with the placebo injection but had a much smaller effect on GADAs, IA2As, and ZnT8As. A total of 40% (19 of 48) of rituximab-treated patients who were IAA positive became IAA negative versus 0 of 29 placebo-treated patients (P 1 year in insulin-treated patients. For the patients receiving insulin for >2 weeks prior to rituximab administration, we cannot assess whether rituximab not only blocks the acquisition of insulin antibodies induced by insulin administration and/or also suppresses preformed insulin autoantibodies. Studies in prediabetic non-insulin-treated patients will likely be needed to evaluate the specific effects of rituximab on levels of IAAs.

Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

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Coiffier, Bertrand; Li, Weimin; Henitz, Erin D; Karkera, Jayaprakash D; Favis, Reyna; Gaffney, Dana; Shapiro, Alice; Theocharous, Panteli; Elsayed, Yusri A; van de Velde, Helgi; Schaffer, Michael E; Osmanov, Evgenii A; Hong, Xiaonan; Scheliga, Adriana; Mayer, Jiri; Offner, Fritz; Rule, Simon; Teixeira, Adriana; Romejko-Jarosinska, Joanna; de Vos, Sven; Crump, Michael; Shpilberg, Ofer; Zinzani, Pier Luigi; Cakana, Andrew; Esseltine, Dixie-Lee; Mulligan, George; Ricci, Deborah

2013-05-01

Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab. ©2013 AACR.

Rituximab-Induced Bronchiolitis Obliterans Organizing Pneumonia

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Ahmet B. Ergin

2012-01-01

Full Text Available Rituximab-induced lung disease (R-ILD is a rare entity that should be considered in patients treated with rituximab who present with dyspnea, fever, and cough, but no clear evidence of infection. A variety of pathologic findings have been described in this setting. Bronchiolitis obliterans organizing pneumonia (BOOP is the most common clinicopathologic diagnosis, followed by interstitial pneumonitis, acute respiratory distress syndrome (ARDS, and hypersensitivity pneumonitis. Prompt diagnosis and treatment with corticosteroids are essential as discussed by Wagner et al. (2007. Here we present a case of an 82-year-old man who was treated with rituximab for recurrent marginal zone lymphoma. After the first infusion of rituximab, he reported fever, chills, and dyspnea. On computed tomography imaging, he was found to have bilateral patchy infiltrates, consistent with BOOP on biopsy. In our patient, BOOP was caused by single-agent rituximab, in the first week after the first infusion of rituximab. We reviewed the relevant literature to clarify the different presentations and characteristics of R-ILD and raise awareness of this relatively overlooked entity.

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON)

DEFF Research Database (Denmark)

Jerkeman, Mats; Eskelund, Christian Winther; Hutchings, Martin

2018-01-01

BACKGROUND: Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data...... performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56...... days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m2) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle...

Radioimmunotherapy using {sup 131}I-rituximab in patients with advanced stage B-cell non-Hodgkin's lymphoma: initial experience

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Bienert, Maren; Reisinger, Ingrid; Humplik, Beatrice I.; Reim, Christel; Kroessin, Thomas; Avril, Norbert; Munz, Dieter L. [Charite - Universitaetsmedizin Berlin, Clinic for Nuclear Medicine, Berlin (Germany); Srock, Stefanie; Pezzutto, Antonio [Charite - Universitaetsmedizin Berlin, Department of Haematology and Oncology, Berlin (Germany)

2005-10-01

The aim of this study was to evaluate the safety, toxicity and therapeutic response of non-myeloablative radioimmunotherapy using {sup 131}I-rituximab in previously heavily treated patients with B-cell non-Hodgkin's lymphoma (B-NHL). Nine patients with relapsed, refractory or transformed B-NHL received ten radioimmunotherapies. Patients had a median of 5 (range 2-7) prior standard therapies. Four patients had received prior high-dose chemotherapy followed by autologous stem cell transplantation, and eight had received prior rituximab therapy. Histopathology consisted of four mantle cell, one follicular and four diffuse large B-cell lymphomas. Rituximab, a monoclonal chimeric anti-CD20 antibody (IDEC-C2B8), was labelled with {sup 131}I using the Iodogen method. The administered activity (2,200{+-}600 MBq) was based on a dosimetrically calculated 45 cGy total-body radiation dose. All patients received an infusion of 2.5 mg/kg of rituximab prior to administration of the radiopharmaceutical. No acute adverse effects were observed after the administration of{sup 131}I-rituximab. Radioimmunotherapy was safe in our patient group and achieved one complete response ongoing at 14 months and two partial responses progressing at 12 and 13 months after treatment. One partial responder was re-treated with radioimmunotherapy and achieved an additional progression-free interval of 7 months. Four non-responders with bulky disease died 4.8{+-}2.0 months after therapy. Three patients had an elevated serum lactate dehydrogenase (LDH) level prior to radioimmunotherapy and none of the patients responded. Of two patients who received radioimmunotherapy as an additional treatment after salvage chemotherapy, one continues to be disease-free at 9 months and one relapsed at 5 months' follow-up. Reversible grade 3 or 4 haematological toxicity occurred in seven of nine patients. Median nadirs were 35 days for platelets, 44 days for leucocytes and 57 days for erythrocytes. (orig.)

Novel antibodies against follicular non-Hodgkin's lymphoma

NARCIS (Netherlands)

van Meerten, Tom; Hagenbeek, Anton

2011-01-01

The anti-CD20 monoclonal antibody rituximab has revolutionized the treatment of patients with follicular B-cell lymphoma. With the combination of chemotherapy and rituximab the overall survival rate has increased with approximately 30%. Unfortunately, there is resistance to rituximab with relapse of

A Case Report of Nongerminal Center B-Cell Type Diffuse Large B-Cell Lymphoma Treated to Complete Response with Rituximab and Ibrutinib

Directory of Open Access Journals (Sweden)

Geoffrey Shouse

2018-01-01

Full Text Available Diffuse large B-cell lymphoma (DLBCL is a molecularly heterogeneous disease consisting of different subtypes with varying clinical behaviors. For example, the activated B-cell-like (ABC type of DLBCL has lower cure rates with traditional chemotherapy regimens. The molecular pathway promoting tumorigenic growth of the ABC type includes a dependence on intracellular signaling by Bruton’s agammaglobulinemia tyrosine kinase (BTK. This specific pathway has led to the investigation of the utility of ibrutinib in treatment of this type of lymphoma at relapse or in combination with standard chemotherapy. In elderly patients stricken with this disease, standard combination chemotherapy can pose significant toxicity. Some reduced intensity regimens have activity but significantly less favorable long-term outcomes and still pose significant toxicity to elderly patients. In the following case, we demonstrate induction of complete response in an elderly patient with significant comorbidities with nongerminal center B-cell type (NGCB DLBCL treated with rituximab, ibrutinib, and prednisone. Toxicity included atrial fibrillation that ultimately led to heart failure as well as sepsis which ultimately led to the patient’s demise. Despite this fact, the response to treatment appeared durable. This case illustrates the utility and limitations of molecularly targeted therapies to treat aggressive lymphoma in frail elderly patients.

Discovery – Development of Rituximab

Science.gov (United States)

NCI funded the development of rituximab, one of the first monoclonal antibody cancer treatments. With the discovery of rituximab, more than 70 percent of patients diagnosed with non-hodgkin lymphoma now live five years past their initial diagnosis.

Novel Combination Chemotherapy for Localized Ewing Sarcoma

Science.gov (United States)

In this clinical trial, researchers will test whether the addition of the drug combination vincristine, topotecan, and cyclophosphamide to a standard chemotherapy regimen improves overall survival in patients with extracranial Ewing

Combined radio- and chemotherapy from the point of view of the internist-oncologist

International Nuclear Information System (INIS)

Engelhardt, R.

1979-01-01

The indications for a combined radio- and chemotherapy can be summarized from three points of view: 1) Intensifying local radiotherapy by chemotherapy. 2) Extending local radiotherapy by systematical chemotherapy. 3) Supporting chemotherapy by radiotherapy. The side effects of the combination are discussed, classified as immediate type and long-term type. It is indicated that in all combinations the drug-specific and/or organ-specific side effects of the cytostatics must be taken into consideration. The substantial therapeutical aspect lies in prophylaxis. Exact data concerning the reduction of the dosage of the radiotherapy and/or the chemotherapy must be found after exact observation of the complications. Knowing the side effects of the immediate-type and taking into consideration the long-term damage which can be expected, there are today clear indications for a combined radio- and chemotherapy. (orig./MG) 891 MG/orig.- 892 RDG [de

Inhibitory effect of sequential combined chemotherapy and radiotherapy on growth of implanted tumor in mice

International Nuclear Information System (INIS)

Okada, Kouji

1983-01-01

Sequential chemotherapy using FT-207, adriamycin and mitomycin C followed by radiotherapy was attempted to achieve effective inhibition against implanted tumor in C57BL/6 black mice bearing YM-12 tumors. Sequential combined chemotherapy was more effective than single drug chemotherapy or combined chemotherapy of other drugs. Addition of radiotherapy to the sequential combined chemotherapy was successful for enhancing therapeutic effect. (author)

A review of topotecan in combination chemotherapy for advanced cervical cancer

Directory of Open Access Journals (Sweden)

Minoo Robati

2008-03-01

Full Text Available Minoo Robati, David Holtz, Charles J DuntonDepartment of Obstetrics and Gynecology, Main Line Gynecologic Oncology, Lankenau Hospital, Wynnewood, PA, USAAbstract: Treatment of advanced, recurrent or persistent cervical cancer includes radiotherapy and chemotherapy. Radiation has been the primary treatment modality for locoregionally advanced cervical cancer. Concomitant systemic cisplatin chemotherapy and radiation have shown high response rates with improvements in durable remissions and overall survival. Cisplatin has been the standard medication for the treatment of advanced cervical cancer. Combinations with other chemotherapeutic agents have been the subject of clinical trials with varying results. The toxicity of combination chemotherapy and tolerability of patients are other factors that should be considered in the management of patients with advanced disease. Recently topotecan, in combination with cisplatin, achieved increased response and overall survival rates without further compromising the patients’ quality of life. This review focuses on the mechanism of action and toxicities of topotecan, as well as its role as a radio-sensitizer and chemotherapeutic agent in the management of advanced, recurrent, or persistent cervical cancer. Other combination modalities and dosages are also discussed.Keywords: topotecan, combination chemotherapy, advanced cervical cancer

A pioneer experience in Malaysia on In-house Radio-labelling of (131)I-rituximab in the treatment of Non-Hodgkin's Lymphoma and a case report of high dose (131)I-rituximab-BEAM conditioning autologous transplant.

Science.gov (United States)

Kuan, Jew Win; Law, Chiong Soon; Wong, Xiang Qi; Ko, Ching Tiong; Awang, Zool Hilmi; Chew, Lee Ping; Chang, Kian Meng

2016-10-01

Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies - (90)Y-ibritumomab tiuxetan is expensive and (131)I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling (131)I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling (131)I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose (131)I-rituximab (6000MBq/163mCi) combined with BEAM conditioning for autologous HSCT. Copyright © 2016 Elsevier Ltd. All rights reserved.

Study on the Preparation and Quality Control of 131I-Rituximab and 90Y-Rituximab for Non-Hodgkin-Lymphoma Therapy

International Nuclear Information System (INIS)

NguyenThi Thu; Duong Van Dong; Vo Thi Cam Hoa; Chu Van Khoa; Bui Van Cuong; Pham Ngoc Dien; Mai Phuoc Tho; Nguyen Thanh Binh; Dang Ho Hong Quang; Phan Quoc Thong; Mai Trong Khoa

2009-01-01

In recent years, radioimmunotherapy (RIT) has become a highly promising oncologic therapeutic modality with established clinically efficacy, particularly in the therapy of haematological malignancies. Rituximab, a chimeric monoclonal antibody targeted against the cluster designation (CD20) antigen was labelled with 131 I used in the treatment of B cell non Hodgkin's Lymphoma (NHL), B cell leukemia. In this study, the monoclonal antibody Rituximab was labelled with 131 I using chloramin T method (ChT). The optimized ChT concentration for the oxidation of 185 MBq of Na 131 I solution and 750□g of Rituximab was 20□g/20□l. The reaction time was 3 minutes at room temperature. The labeling reaction has stopped using sodiummetabisulphite (SMB). Labelling efficacy was controlled by ITLC. The reaction mixture was purified through the Sephadex G-25 PD10 Pharmacia column. The collected 131 I-Rituximab was filtered through a 0.20'm milipore sterile filter. The radiochemical labeling yield was more than 95%. Radiochemical purity of the radiopharmaceutical after purification was more than 99%. The product has been passed the test for sterility, bacterial endotoxins, to be sufficiency invivo and invitro stable and stability after labeling. 131 I-Rituximab was used for radioimmunoscintigraphy biodistribution in clinical. Rituximab was bound to the DTPA chelating agent using Hnatowich methods. Cyclic anhydride DTPA (cDTPAa, 0.1 mg/ml) was dissolved in chloroform and was degassed under a stream of nitrogen for 30 min. Rituximab solution in 0.05M bicarbonate buffer was immediately added and mixed for one minute at room temperature. The antibody Rituximab at different concentration (5mg/ml and 10mg/ml) was coupled with the cyclic DTPA anhydride, at molar ratios (cDTPAa : Rituximab) of 1:1, 3:1, 5:1, 10:1 and 20:1. The conjugation DTPA-Rituximab mixture was labelled with Y- 90 and purified and determinate of coupling efficiency. Coupling efficiency of cDTPA - to - Rituximab molar

Combined radiotherapy-chemotherapy in clinical practice

International Nuclear Information System (INIS)

Horwich, A.

1989-01-01

This paper investigates the combination of radiotherapy and chemotherapy performed over the last 15 years. The improvement of the therapeutic ratio of anti- cancer effect to normal tissue toxicity and its requirement of a thorough understanding of the biological effects of each modality and of how these effects may interact is presented. Early studies and conclusions are examined

Rituximab-related viral infections in lymphoma patients.

Science.gov (United States)

Aksoy, Sercan; Harputluoglu, Hakan; Kilickap, Saadettin; Dede, Didem Sener; Dizdar, Omer; Altundag, Kadri; Barista, Ibrahim

2007-07-01

Recently, a human/mouse chimeric monoclonal antibody, rituximab, has been successfully used to treat cases of B-cell non-Hodgkin's lymphoma and some autoimmune diseases. However, several viral infections related to rituximab have been reported in the literature, but were not well characterized. To further investigate this topic, relevant English language studies were identified through Medline. There were 64 previously reported cases of serious viral infection after rituximab treatment. The median age of the cases was 61 years (range: 21 - 79). The median time period from the start of rituximab treatment to viral infection diagnosis was 5.0 months (range: 1 - 20). The most frequently experienced viral infections were hepatitis B virus (HBV) (39.1%, n = 25), cytomegalovirus infection (CMV) (23.4%, n = 15), varicella-zoster virus (VZV) (9.4%, n = 6), and others (28.1%, n = 18). Of the patients with HBV infections, 13 (52.0%) died due to hepatic failure. Among the 39 cases that had viral infections other than HBV, 13 died due to these specific infections. In this study, about 50% of the rituximab-related HBV infections resulted in death, whereas this was the case in only 33% of the cases with other infections. Close monitoring for viral infection, particularly HBV and CMV, in patients treated with rituximab should be recommended.

Malignant cliomas treated after surgery by combination chemotherapy and delayed irradiation. Pt. 1

International Nuclear Information System (INIS)

Poisson, M.; Mashaly, R.; Pertuiset, B.F.; Metzger, J.

1979-01-01

Forty-six patients with gliomas were introduced after surgery into a therapeutic programme of six cycles of combination chemotherapy with VM 26 and CCNU, followed by delayed irradiation six months after surgery with an average dose of 5,800 rads. After irradiation the same preradiation chemotherapy was readministered for an average of four cycles. The results were compared to those from another group of 28 patients treated only by the same chemotherapy (CRC and C groups successively). Twelve patients (26%) died before irradiation in the CRC groups, six patients (13%) had recurrences at the time of irradiation, and 28 patients (61%) had no clinical or radiological signs of recurrence at the time of irradiation. For the total of treated patients the median survival after surgery was 17 months, and 46% of the patients were surviving at 18 months. The percentage of survivors at 18 months was significantly more elevated in the group treated by combination chemotherapy and delayed irradiation than in a control group treated by the same combination chemotherapy alone. This result suggests that in approximately 50% of cases combination chemotherapy after surgery, and delayed irradiation six months after surgery, cumulated their effects on survival time. (author)

A pioneer experience in Malaysia on In-house Radio-labelling of "1"3"1I-rituximab in the treatment of Non-Hodgkin's Lymphoma and a case report of high dose "1"3"1I-rituximab-BEAM conditioning autologous transplant

International Nuclear Information System (INIS)

Kuan, Jew Win; Law, Chiong Soon; Wong, Xiang Qi; Ko, Ching Tiong; Awang, Zool Hilmi; Chew, Lee Ping; Chang, Kian Meng

2016-01-01

Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies – "9"0Y-ibritumomab tiuxetan is expensive and "1"3"1I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling "1"3"1I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling "1"3"1I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose "1"3"1I-rituximab (6000 MBq/163 mCi) combined with BEAM conditioning for autologous HSCT. - Highlights: • Usual dose: Day 0 (dosimetry) – 5 mCi, Day 7 (therapeutic) 0.75 Gy to whole body. • High dose: 6000 MBq (163 mCi) on Day − 18, BEAM conditioning starts on Day − 8. • Self-labelled "1"3"1I-rituximab is a viable treatment in resource limited environment. • "1"3"1I-rituximab may substitute autologous transplant. • High dose "1"3"1I-rituximab-BEAM is a feasible conditioning regime.

Enfermedad pulmonar intersticial asociada a rituximab

Directory of Open Access Journals (Sweden)

Marcelo Fernández Casares

2013-08-01

Full Text Available La introducción en la práctica clínica del anticuerpo anti-CD20 rituximab ha mejorado sustancialmente el pronóstico de diversas enfermedades autoinmunes y hematológicas. Con el incremento de su uso ha aumentado el registro de efectos adversos, entre ellos la toxicidad pulmonar. Una de sus complicaciones más serias es la enfermedad pulmonar intersticial, entidad potencialmente fatal que debe ser considerada en pacientes que han recibido rituximab y presentan disnea, fiebre y tos sin clara evidencia de infección. Presentamos un caso de enfermedad pulmonar intersticial asociada a rituximab.

Role of combination chemotherapy in non-Hodgkin's lymphoma in children

International Nuclear Information System (INIS)

Dutta, H.S.; Chandra, A.B.; Mitter, M.; Mukherjee, D.; Batabyal, S.; Samaddar, A.S.; Mukherjee, S.

1980-01-01

Eighteen children suffering from Non-Hodgkin's lymphoma were studied. Of these eighteen children, eight (44.4 percent) had well differentiated diffuse lymphocytic lymphoma and six (33.3 percent) had poorly differentiated diffuse lymphocytic lymphoma and four (22.3 percent) had histiocytic lymphoma. Histological study was based on the concept of Rappaport (1966). Children belonging to Stage IIB were treated with radiotherapy followed by combination chemotherapy and those with Stage IIIB and Stage IVB were treated with combination chemotherapy utilising cyclophosphamide, oncovin and prednisolone. The result of combination chemotherapy (COP) was dramatic and appears to have resulted in long term disease free survival. In well differentiated diffuse lymphocytic lymphoma in Stage IIB the life expectancy of two children was extended to 12 years with well maintained remission for 9.5 years. Recurrence rate was 44.4 percent. Death rate was 61.1 percent and median survival time was 26.7 months. In histiocytic lymphomas the results were unsatisfactory. Median survival time was 9.5 months. (author)

Super-selective interventional chemotherapy combined with systemic chemotherapy for the treatment of postoperative gliomas:a clinical study

International Nuclear Information System (INIS)

Chen Jian; Hu Qinglei; Sun Yanchun; Feng Lei; Liu Yunzhen; Liu Ju; Kong Ruifen

2010-01-01

Objective: To evaluate super-selective interventional chemotherapy combined with systemic chemotherapy in treating postoperative gliomas. Methods: During the period of 2005-2009, a total of 46 patients with glioma were encountered in our hospital. According to the principle of patient's free will the involved patients were divided into two groups. Study group (n = 25): after operation the patients received routine radiotherapy, which was followed by super-selective interventional chemotherapy combined simultaneously with systemic chemotherapy. Control group (n = 21): after operation the patients received routine radiotherapy, which was followed by systemic chemotherapy only. The patients were regularly followed up. Cranial CT checkups were made to determine the tumor size, and the results were evaluated with Karnofsky scores. The clinical data were analyzed and compared between two groups. Results: In the study group, the side-effects and complications included epileptic seizures (n = 3), eye pain (n = 5), headache (n = 9), nausea and vomiting (n = 8) and thrombopenia (n = 1). In the control group,the side-effects and complications were as follows: epileptic seizures (n = 1), headache (n = 7), nausea and vomiting (n = 6) and thrombopenia(n = 3). No death occurred in either of the two groups. The patients were followed up for an average period of 2.3 years. Before chemotherapy no statistically significant difference in tumor size existed between two groups (P > 0.05). One year after the chemotherapy, the tumor volume in study group was reduced by 67.11%, while it was 45.79% in control group. By using independent sample t test analysis, the difference between two groups was of statistical significance (P < 0.05). Wilcoxon rank sum test and Karnofsky prognostic score analysis indicated that the prognosis of study group was much better than that of control group (P < 0.05). Conclusion: In comparison with routine radiotherapy plus simple systemic chemotherapy, routine

Rituximab for nephrotic syndrome in children.

Science.gov (United States)

Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai

2017-04-01

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. At least 20 % of children with this syndrome show frequent relapses and/or steroid dependence during or after immunosuppressive therapies, a condition defined as complicated frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS). Approximately 1-3 % of children with idiopathic nephrotic syndrome are resistant to steroids and all immunosuppressive agents, a condition defined as refractory steroid-resistant nephrotic syndrome (SRNS); these SRNS children have a high risk of end-stage renal failure. Rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to be effective for patients with complicated FRNS/SDNS and refractory SRNS. This review describes the recent results of rituximab treatment applied to pediatric nephrotic syndrome, as well as those of our recent study, a multicenter, double-blind, randomized, placebo-controlled trial of rituximab for childhood-onset complicated FRNS/SDNS (RCRNS01). The overall efficacy and safety of rituximab for this disease are discussed.

Desensitization to rituximab in a multidisciplinary setting.

Science.gov (United States)

Amorós-Reboredo, Patrícia; Sánchez-López, Jaime; Bastida-Fernández, Carla; do Pazo-Oubiña, Fernando; Borràs-Maixenchs, Núria; Giné, Eva; Valero, Antonio; Creus-Baró, Natàlia

2015-10-01

The need to offer first-line therapy to the increasing number of patients who have suffered an hypersensitivity reaction has stimulated the use of rapid desensitization protocols. To present our experience working as a multidisciplinary team using a rituximab rapid desensitization scheme. Patient demographics, allergic reaction, skin tests to rituximab, number of desensitizations, reactions during the desensitization protocol and actions taken, number of administered and completed cycles, were retrospectively collected in patients who received at least one desensitization to rituximab. Number of desensitizations successfully managed. Between 2012 and June 2013 five patients received a total of 19 desensitizations to rituximab using a 12 step rapid desensitization protocol. All patients received the scheduled chemotherapeutic cycles as inpatients, with no delay in administration dates. Three patients presented a hypersensitivity reaction during the first desensitization and in one patient the event occurred again during the second treatment cycle. All reactions occurred in the last step, when the infusion rate reached the maximum speed. The developed protocol for rapid desensitization was successful in five patients receiving rituximab. Patients could receive the full intended dose.

[Effects of pamidronate disodium (Bonin) combined with chemotherapy on bone pain in multiple myeloma].

Science.gov (United States)

Leng, Yun; Chen, Shi-lun; Shi, Hong-zhi

2002-10-01

Objective. To evaluate the therapeutic effects of Disodium Pamidronate (Bonin) on bone pain in multiple myeloma. Method. 18 patients received only chemotherapy and 16 patients with addition of Bonin were compared. Result. The bone pain was significantly relieved both in chemotherapy alone group and in the combination group of Bonin with chemotherapy after treatment (P<0.01, as compared with before therapy). However, the effects of combination group were more dramatical than that of the other group (P<0.05). No obvious side-effects were observed except mild fever in one patient in the combination group. Conclusion. Bonin, as a safe and effective Bisphosphonates preparation, could relieve bone pain in multiple myeloma more effectively when combined with chemotherapy.

Lupus nephritis, pregnancy and rituximab

Directory of Open Access Journals (Sweden)

Enrique Dorado

2017-04-01

Full Text Available La nefritis lúpica (NL proliferativa es una de las complicaciones más graves del LES. La respuesta terapéutica con los esquemas clásicos no existe en el 20 al 70% de los casos, siendo la amplitud de dicho rango explicada por variaciones étnicas, falta de consenso en la definición de remisión, diferencias en los tiempos de tratamiento, seguimiento y en la clase de NL. En presencia de NL recidivante o refractaria los tratamientos y el nivel de evidencia sobre su eficacia son más limitados. Rituximab es un anticuerpo monoclonal quimérico (ratón-humano dirigido contra el antígeno CD 20 localizado en la superficie celular de los linfocitos B. Estos participan en la patogénesis del LES a partir de su maduración en células plasmáticas, producción de anticuerpos, secreción de citoquinas proinflamatorias, presentación de autoantígenos a las células T y en la activación de células T. La administración de rituximab genera un rápido y sostenido descenso de los linfocitos B CD 20+ circulantes y una reducción de los títulos de auto-anticuerpos. Se reportó una disminución significativa en los niveles de antiDNA a partir de la semana 14 y de los niveles de IgM, sin compromiso de IgG ni de IgA. Se detectó droga activa en sangre periférica luego de la semana 24 de la última infusión. La depleción de linfocitos B se puede mantener por 6 meses, su reconstitución es heterogénea y puede tardar más de un año. Esta linfopenia selectiva tendría un valor predictivo de respuesta terapéutica, la remisión clínica prolongada tendría asociación con repoblación incompleta de células B de memoria varios años luego del tratamiento. En estudios observacionales realizados en pacientes con NL refractaria se reportó respuesta terapéutica con rituximab entre 67-77 % luego de 6 a 12 meses de seguimiento. Sin embargo los resultados del estudio Lupus Nephritis Assesment with Rituximab (LUNAR, randomizado controlado, a doble ciego

Clinical evaluation of rituximab treatment for neuromyelitis optica.

Science.gov (United States)

Fernández-Megía, M J; Casanova-Estruch, B; Pérez-Miralles, F; Ruiz-Ramos, J; Alcalá-Vicente, C; Poveda-Andrés, J L

2015-10-01

Neuromyelitis optica is an inflammatory and usually relapsing demyelinating autoimmune disease of the central nervous system that targets the optic nerves and spinal cord. Rituximab has been used for different neurological diseases that are probably immune-mediated or involving humoural immunity. The objective of this study is to evaluate the efficacy and safety of rituximab as treatment for neuromyelitis optica in a tertiary hospital. Retrospective study of patients with neuromyelitis optica treated with rituximab 1000mg on days 1 and 15, repeated every 6 to 8 months. We recorded EDSS score, relapse rate, overall condition, CD19+ count, presence of anti-NMO antibodies, and possible adverse reactions. Six patients were treated; all were women with a median age of 46 years (range, 38-58). Anti-NMO antibodies were detected in 3 patients (50%). Baseline EDSS was 4 (range 2.0-5.5). Two patients had previously been treated with an immunomodulatory drug. Median time from the first rituximab infusion to first relapse was 3.7 years (range 1.7-6.9). Two patients had infusion reactions after the first dose of rituximab. Four patients remained relapse-free and their EDSS score did not progress during rituximab treatment, one patient showed no clinical improvement, and one patient could not be evaluated. Rituximab can be considered an attractive therapeutic alternative for patients with neuromyelitis optica as there are no approved treatments for this disease. Further studies with rituximab are needed to establish the role of this drug in treating neuromyelitis optica. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Detection and quantification of rituximab in the human urine.

Science.gov (United States)

Jacobs, Roland; Langer-Jacobus, Thais; Duong, Michelle; Stahl, Klaus; Haller, Hermann; Schmidt, Reinhold E; Schiffer, Mario

2017-12-01

B cell depletion by rituximab treatment might be inefficient in patients suffering from nephrotic syndrome. Due to the impaired glomerular filtration barrier a significant portion of the therapeutic antibody might be lost into the urinary space. In order to determine the amount of rituximab in the urine of such patients, CD20+ Daudi cells were stained with the patients' urine followed by a fluorochrome-labeled secondary antibody. Mean fluorescence intensity of that way labeled Daudi cells was determined by flow cytometry. Control samples with defined rituximab concentrations were used to create standard curves. The analyses revealed that all nephelometric IgG+ urine samples tested also manifested rituximab at concentrations between 100 and 46,707μg/L. The flow cytometry-based approach is an easy and reliable method to assess rituximab in patients' urine samples for monitoring individual rituximab treatment courses in all patients co-presenting impaired renal filtration. Presence of such antibodies in the urine could be considered as criteria to modify the formulation or modality of rituximab delivery in order to prevent the loss of the therapeutic antibodies and thereby ensuring efficacy of the therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

A case of "refractory" lupus erythematosus profundus responsive to rituximab [case report].

LENUS (Irish Health Repository)

McArdle, Adrian

2012-02-01

Lupus erythematosus profundus is a rare complication of systemic lupus erythematosus characterized by the presence of deep, tender subcutaneous nodules. A 22-year-old African-American female with extensive lupus profundus resistant to conventional therapies was treated with two infusions of the anti-CD20 monoclonal antibody, rituximab, at a dosage of 1,000 mg each. The patient demonstrated a remarkable clinical response as indicated by the disappearance of the nodules. B-cell depletion therapy with rituximab used alone or in combination with other therapies may be a viable option in patients with lupus profundus refractory to current therapies.

The combination of chemotherapy and radiotherapy towards more efficient drug delivery.

Science.gov (United States)

Cao, Wei; Gu, Yuwei; Meineck, Myriam; Xu, Huaping

2014-01-01

Research on anticancer therapies has advanced significantly in recent years. New therapeutic platforms that can further improve the health of patients are still highly demanded. We propose the idea of combining regular chemotherapy with radiation therapy to minimize side effects as well as increase drug-delivery efficiency. In this Focus Review, we seek to provide an overview of recent advances that can combine chemotherapy and radiotherapy. We begin by reviewing the current state of systems that can combine chemotherapy and gamma radiation. Among them, diselenide-containing polymers are highlighted as sensitive drug-delivery vehicles that can disassemble under gamma radiation. Then X-ray responsive materials as promising alternative systems are summarized, including X-ray responsive drug-delivery vehicles, prodrugs that can be activated by X-rays, and radiation-site-targeting systems. Finally, we describe strategies that involve phototherapies. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.

Directory of Open Access Journals (Sweden)

Øystein Fluge

Full Text Available Chronic fatigue syndrome (CFS is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti-CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients.In this double-blind, placebo-controlled phase II study (NCT00848692, 30 CFS patients were randomised to either Rituximab 500 mg/m(2 or saline, given twice two weeks apart, with follow-up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV was not detected in any of the patients. The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67% in the Rituximab group and in two out of 15 patients (13% in the Placebo group (p = 0.003. Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44. Four Rituximab patients had clinical response durations past the study period. General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed, with differences between the Rituximab and Placebo groups between 6-10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative. There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening.The delayed responses starting from 2-7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses. The present findings will impact

Preclinical safety, pharmacokinetics, pharmacodynamics, and biodistribution studies with Ad35K++ protein: a novel rituximab cotherapeutic

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Maximilian Richter

2016-01-01

Full Text Available Rituximab is a mouse/human chimeric monoclonal antibody targeted toward CD20. It is efficient as first-line therapy of CD20-positive B-cell malignancies. However, a large fraction of treated patients relapse with rituximab-resistant disease. So far, only modest progress has been made in treatment options for rituximab refractory patients. One of the mechanisms for rituximab resistance involves the upregulation of CD46, which is a key cell surface protein that blocks the activation of complement. We have recently developed a technology that depletes CD46 from the cell surface and thereby sensitizes tumor cells to complement-dependent cytotoxicity. This technology is based on a small recombinant protein, Ad35K++ that binds with high affinity to CD46. In preliminary studies using a 6 × histidinyl tagged protein, we had demonstrated that intravenous Ad35K++ injection in combination with rituximab was safe and increased rituximab-mediated killing of CD20-positive target cells in mice and nonhuman primates (NHPs. The presence of the tag, while allowing for easy purification by Ni-NTA chromatography, has the potential to increase the immunogenicity of the recombinant protein. For clinical application, we therefore developed an Ad35K++ protein without His-tag. In the present study, we performed preclinical studies in two animal species (mice and NHPs with this protein demonstrating its safety and efficacy. These studies estimated the Ad35K++ dose range and treatment regimen to be used in patients. Furthermore, we showed that intravenous Ad35K++ injection triggers the shedding of the CD46 extracellular domain in xenograft mouse tumor models and in macaques. Shed serum CD46 can be measured in the serum and can potentially be used as a pharmacodynamic marker for monitoring Ad35K++ activity in patient undergoing treatment with this agent. These studies create the basis for an investigational new drug application for the use of Ad35K++ in combination with

Clinical research on cancer treatment with combined radiotherapy and chemotherapy

International Nuclear Information System (INIS)

Fuwa, Nobukazu; Ito, Yoshiyuki; Kato, Eriko; Koyama, Kazuyuki; Morita, Kozo

1993-01-01

There are two purposes of using combined chemotherapy and radiotherapy in the treatment of cancers. One is to suppress distant metastasis, especially micrometastasis; the other is to improve localized control. As a trial of the utility of the former, systemic chemotherapy with CDDP and 5 FU was given successively with radiotherapy to treat nasopharyngeal cancer. The survival rate was significantly improved compared with historical control cases. The main reason for this effectiveness was the improvement of localized control. The suppression of distant metastasis is the subject of future research. As a trial of the utility of the latter, a super-selective intraarterial chemotherapy with CBDCA combined with radiotherapy was used to head and neck localized progressive cancers. The control of localized cancer was remarkably effective. This treatment is considered to be especially suitable for locally advanced tongue cancer and cancer of the root of the tongue. (author)

Study on combined chemotherapy and radiotherapy of the microcellular bronchial carcinoma (CCR study): chemo-/radiotherapy opposed to radio-/chemotherapy

International Nuclear Information System (INIS)

Heilmann, H.P.; Buenemann, H.; Arnal, M.L.; Calavrezos, A.; Engel, J.; Hain, E.; Koschel, G.; Seysen, U.; Allgemeines Krankenhaus Harburg, Hamburg; Franke, H.D.; Juengst, G.; Kohl, F.V.; Wichert, P. v.

1983-01-01

The authors studied the effect of a chemo-/radiotherapy or radio-/chemotherapy on 52 cases of microcellular bronchial carcinoma, classification ''limited disease''. The survival curves were slightly better for the patients submitted to primary chemotherapy, but the difference was not statistically significant, and the curves coincided again after 18 months. 60 to 80% of the patients had no complaints or only unimportant complaints during more than half of their survival time. In 23 patients with ''extensive disease'' who received only a symptomatic therapy or a combined palliative chemotherapy, chemotherapy had a slightly better effect, but this was not statistically significant. (orig.) [de

Oral combination chemotherapy in the treatment of AIDS ...

African Journals Online (AJOL)

Objectives: To determine the effectiveness of an oral combination chemotherapy regimen administered to patients with AIDS-associated Hodgkin's disease. Design: Prospective, pilot phase II clinical trial. Setting: Consecutive patient recruitment occurred at two medical centers in the United States: Albany Medical Center, ...

Chemotherapy response as a prognosticator for survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

International Nuclear Information System (INIS)

Eagan, R.T.; Fleming, T.R.; Lee, R.E.; Ingle, J.N.; Frytak, S.; Creagan, E.T.

1980-01-01

Twenty-two patients with limited unresectable squamous cell lung cancer were treated with 6 courses of combination chemotherapy consisting of cyclophosphamide, adriamycin, cisplatin, and bleomycin (CAP-Bleo) and short-course thoracic irradiation started after the first 4 weeks of chemotherapy. Of 20 patients with visible tumor who were treated with 4 weeks of chemotherapy alone, 10 (50%) had a tumor regression in that 4 week period and 10 did not. Those patients with tumor regression had significantly better progression free and overall survivals than did patients with no chemotherapy regressions (medians of 258 days vs. 136 days and 356 days vs. 150 days respectively). The original bleomycin dose had to be reduced by 50% primarily because of excessive radiation esophagitis that has not been reported with use of either the CAP regimen or bleomycin along in conjunction with thoracic irradiation. An initial chemotherapy regression seems to be a good prognosticator for progression-free and overall survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

Combined radiation therapy and intraarterial chemotherapy for advanced oral or oropharngeal carcinoma

International Nuclear Information System (INIS)

Okawa, Tomohiko; Kita, Midori; Tanaka, Makiko; Ishii, Tetsuo

1989-01-01

During the period 1982-1988, 34 patients with advanced oral or oropharyngeal carcinoma were treated with radical radiation therapy combined with intraarterial chemotherapy. Five patients were clinically staged as Stage II,15 as Stage III, and 14 as Stage IV. For intraarterial chemotherapy, ACNU (25mg/body) or CDDP (20 mg/m 2 ) plus MMC (6 mg/m 2 ) was used. Overall, the complete response rate was 56%: it was independent of the site of carcinoma, clinical stage, and the kind of drugs. The two-year cumulative survival rate was 80% for Stage II, 56% for Stage III, and 61% for Stage IV. Side effects were not so severe as to continue with the withdrawal of chemotherapy. In view of the efficacy and safety, combined radiation therapy and intraarterial chemotherapy should be performed in the treatment of oral or oropharyngeal carcinoma. (N.K.)

Dexamethasone, Intravenous Immunoglobulin, and Rituximab Combination Immunotherapy for Pediatric Opsoclonus-Myoclonus Syndrome.

Science.gov (United States)

Pranzatelli, Michael R; Tate, Elizabeth D

2017-08-01

Although pulse-dose dexamethasone is increasingly favored for treating pediatric opsoclonus-myoclonus syndrome (OMS), and multimodal immunotherapy is associated with improved clinical response, there have been no neuroimmunologic studies of dexamethasone-based multimodal disease-modifying therapy. In this observational retrospective study, 19 children with OMS (with or without associated neuroblastoma) underwent multibiomarker evaluation for neuroinflammation. Nine children of varying OMS severity, duration, and treatment status were treated empirically with pulse dexamethasone, intravenous immunoglobulin (IVIg), and rituximab combination immunotherapy (DEXIR-CI). Another 10 children on dexamethasone alone or with IVIg at initial evaluation only provided a comparison group. Motor severity (total score) was scored rater-blinded via videotapes using the validated OMS Evaluation Scale. DEXIR-CI was associated with a 69% reduction in group total score (P = 0.004) and was clinically well tolerated. Patients given the dexamethasone combination exhibited significantly lowered B cell frequencies in cerebrospinal fluid (-94%) and blood (-76%), normalizing the cerebrospinal fluid B cell percentage. The number of patients with positive inflammatory markers dropped 87% (P = 0.002) as did the number of markers. Cerebrospinal fluid oligoclonal bands were positive in four of nine pretreatment patients but zero of six post-treatment patients. In the comparison group, partial response to dexamethasone alone or with IVIg was associated with multiple positive markers for neuroinflammation despite an average of seven months of treatment. Multimechanistic dexamethasone-based combination immunotherapy increases the therapeutic armamentarium for OMS, providing a viable option for less severely affected individuals. Partial response to dexamethasone with or without IVIg is indicative of ongoing neuroinflammation and should be treated promptly and accordingly. Copyright © 2017

Rituximab: An emerging therapeutic agent for kidney transplantation

Directory of Open Access Journals (Sweden)

Joseph Kahwaji

2009-10-01

Full Text Available Joseph Kahwaji, Chris Tong, Stanley C Jordan, Ashley A VoComprehensive Transplant Center, Transplant immunology Laboratory, HLA Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USAAbstract: Rituximab (anti-CD20, anti-B-cell is now emerging as an important drug for modification of B-cell and antibody responses in solid-organ transplant recipients. Its uses are varied and range from facilitating desensitization and ABO blood group-incompatible transplantation to the treatment of antibody-mediated rejection (AMR, post-transplant lymphoproliferative disorder (PTLD, and recurrent glomerular diseases in the renal allograft. Despite these uses, prospective randomized trials are lacking. Only case reports exist in regards to its use in de novo and recurrent diseases in the renal allograft. Recent reports suggests that the addition of rituximab to intravenous immunoglobulin (IVIG may have significant benefits for desensitization and treatment of AMR and chronic rejection. Current dosing recommendations are based on data from United States Food and Drug Administration-approved indications for treatment of B-cell lymphomas and rheumatoid arthritis. From the initial reported experience in solid organ transplant recipients, the drug is well tolerated and not associated with increased infectious risks. However, close monitoring for viral infections is recommended with rituximab use. The occurrence of progressive multifocal leukoencephalopathy (PML has been reported with rituximab use. However, this is rare and not reported in the renal transplant population. Here we will review current information regarding the effectiveness of rituximab as an agent for desensitization of highly human leukocyte antigen-sensitized and ABO-incompatible transplant recipients and its use in treatment of AMR. In addition, the post-transplant use of rituximab for treatment of PTLD and for recurrent and de novo glomerulonephritis in the allograft will be discussed. In

Rituximab in treatment of idiopathic glomerulopathy

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Kamel El-Reshaid

2012-01-01

Full Text Available The aim of our study was to assess the role of rituximab (Mabthera in the treatment of patients with corticosteroid-resistant and calcineurin-inhibitors ± cellcept refractory idiopathic nephrotic syndrome (INS. A total of 83 patients who had required the previous treatment for a minimum of two years were included in the study. Our protocol included the use of rituximab in four-weekly slow infusions. Five patients were excluded as they could not tolerate rituximab infusion for allergic reaction. As expected, none of the patients had a decline in the total circulating lymphocyte counts yet all had achieved decline of their initially normal CD20 to < 0.5% one month after infusion. The decline persisted for eight to ten months later. In the minimal change disease (MCD group, 31 of the 32 patients had complete remission (CR and were off any immunosuppressive therapy and one of the previous non-responders (NR did not respond. Excluding two patients who had required retreatment, the others remained in CR (17 up to 28 months and six up to 36 months. Treatment with rituximab resulted in amelioration of NS in 17 of the 18 patients with focal segmental glomerulosclerosis (FSGS, while only one patient remained NR. Although renal function remained stable, proteinuria reappeared by eight to 12 months. Retreatment with rituximab resulted in a similar response with stable kidney function. In the 28 patients with membranous glomerulopathy (MG, 24 had achieved CR. Two patients failed to respond and two had partial remission. By 12 months, all patients relapsed. The response was within one month following treatment in patient with MCD, but was gradual within three months in FSGS and MG. Relapsers in all groups responded in a similar pattern to repeat dosing with the drug subsequently. Our prospective study represents an adequate number of patients with biopsy-proven subgroups of INS in both children and adults with long-term follow-up of treatment with rituximab

B Cell Depletion: Rituximab in Glomerular Disease and Transplantation

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S. Marinaki

2013-12-01

Full Text Available B cells play a central role in the pathogenesis of many autoimmune diseases. Selective targeting can be achieved with the use of the monoclonal antibody rituximab. In addition to being a drug for non-Hodgkin's lymphoma, rituximab is also an FDA-approved treatment for refractory rheumatoid arthritis and, since recently, ANCA vasculitis. It has shown efficacy in many autoimmune diseases. This review will discuss current evidence and the rationale of the use of rituximab in glomerular diseases, including randomized controlled trials. The focus will be on the use of rituximab in idiopathic membranous nephropathy, systemic lupus erythematosus and ANCA-associated vasculitis. The emerging role of rituximab in renal transplantation, where it seems to be important for the desensitization protocols for highly sensitized patients as well as for the preconditioning of ABO-incompatible recipients and the treatment of antibody-mediated rejection, will also be addressed.

Combination therapy with rituximab, low-dose cyclophosphamide, and prednisone for idiopathic membranous nephropathy: a case series.

Science.gov (United States)

Cortazar, Frank B; Leaf, David E; Owens, Charles T; Laliberte, Karen; Pendergraft, William F; Niles, John L

2017-02-01

Membranous nephropathy is a common cause of the nephrotic syndrome. Treatment with standard regimens fails to induce complete remission in most patients. We evaluated the efficacy of combination therapy with rituximab, low-dose, oral cyclophosphamide, and an accelerated prednisone taper (RCP) for the treatment of idiopathic membranous nephropathy. We analyzed 15 consecutive patients with idiopathic membranous nephropathy treated with RCP at Massachusetts General Hospital. Seven patients (47%) received RCP as initial therapy, and the other eight patients (53%) received RCP for relapsing or refractory disease. All patients had at least 1 year of follow-up. The co-primary outcomes were attainment of partial and complete remission. Partial remission was defined as a urinary protein to creatinine ratio (UPCR) RCP resulted in high rates of complete remission. Larger studies evaluating this regimen are warranted.

Rituximab Therapy for Severe Cutaneous Leukocytoclastic Angiitis Refractory to Corticosteroids, Cellcept and Cyclophosphamide

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Kamel El-Reshaid

2013-04-01

Full Text Available We report our clinical experience with rituximab in the treatment of 2 patients with idiopathic cutaneous angiitis who relapsed after treatment with high-dose corticosteroids and cyclophosphamide. A 39-year-old woman and a 51-year-old man presented with ulcerating maculopapular rash in both lower limbs which relapsed 6 months after treatment with a combination of high-dose corticosteroids and cyclophosphamide. After treatment with 2 g of rituximab, the first patient has still been in clinical remission for 32 months while the second has finished 28 months. Interestingly, CD19 which had dropped to 0.5% 8 months later in both patients. Despite that, our patients are still in clinical remission. No significant side effects were noted during infusions and up to the period of follow-up. In conclusion, rituximab is a useful and safe agent in the treatment of idiopathic cutaneous angiitis refractory to conventional therapy. Clinical remission persists years after improvement of B-cell suppression.

Histopathologic findings of radiotherapy combined with chemotherapy on head and neck cancer

International Nuclear Information System (INIS)

Sakaino, Koji; Matsumoto, Mitsuomi; Satake, Bunsuke; Takahashi, Keiichi; Makino, Sotaro

1979-01-01

We studied in this series about histopathologic changes in radiotherapy of squamous cell carcinoma of head and neck. Then we recognized that radiotherapy combined with chemotherapy is useful for radioresistant squamous cell carcinoma. In this series, we studied about cancer of the tongue as one of the keratinizing squamous cell carcinoma and used Bleomycin as a chemotherapeutic drug. We commented as follows: 1. Radiotherapy combined with chemotherapy had benefit decreasing of a period for radium therapy. 2. Severs complication was not occurred in this series, then this combined therapy was useful for aged or handicapped patient. (author)

Addition of rituximab to chemotherapy overcomes the negative prognostic impact of cyclin E expression in diffuse large B-cell lymphoma

DEFF Research Database (Denmark)

Frei, E; Visco, C; Xu-Monette, Z Y

2013-01-01

High levels of cyclin E (CCNE) are accompanied by shorter survival in cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP)-treated diffuse large B-cell lymphomas (DLBCL), independent of the international prognostic index (IPI). Data on the prognostic role of CCNE in the 'rituximab...

Clinical application of radiotherapy combined with chemotherapy

International Nuclear Information System (INIS)

Morita, Kozo

1978-01-01

In clinical application of radiation therapy combined with chemotherapy, it is important to gain the maximal therapeutic benefit. At present we have no agents that improve the therapeutic ratio by enhancing the effect of radiation on the tumor cell selectively. Therefore, it is necessary to use combining some or all of following procedures: (1) the intraarterial infusion of the agents, (2) the selective localization by reason of the biological affinity of the agents, (3) the surgical removal of the non-sensitized tumor residue and (4) the selective sensitization of the tumor due to its shorter cell cycle. (author)

Combined modality treatment with radiotherapy and chemotherapy

International Nuclear Information System (INIS)

Tannock, I.F.; Toronto Univ., ON

1989-01-01

The present paper discusses some of the methodological issues which can confound the interpretation of clinical trials of combined modality treatment. It reviews some of the larger randomized trials which have evaluated combined modality treatment in cancers of the head and neck, lung, gastrointestinal tract and bladder. It concludes that adequate trials have yet to be performed in many of thses sites, but that at present, evidence for long-term benefit from adjunctivechemotherapy is meagre. Finally, it suggests some possible mechanisms which might heve limited the benefit of chemotherapy when added to radiation treatment. (Author). 87 refs.; 4 figs.; 4 tabs

Intravenous chemotherapy combined with intravesical chemotherapy to treat T1G3 bladder urothelial carcinoma after transurethral resection of bladder tumor: results of a retrospective study

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Zhang Y

2016-01-01

Full Text Available Yu Zhang,1,* Linguo Xie,1,* Tao Chen,1,* Wanqin Xie,2 Zhouliang Wu,1 Hao Xu,1 Chen Xing,1 Nan Sha,1 Zhonghua Shen,1 Yunkai Qie,1 Xiaoteng Liu,1 Hailong Hu,1 Changli Wu1 1Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, 2Key Laboratory of Genetics and Birth Health of Hunan Province, The Family Planning Research Institute of Hunan Province, Changsha, People’s Republic of China *These authors contributed equally to this work Objective: The management of stage 1 and grade 3 (T1G3 bladder cancer continues to be controversial. Although the transurethral resection of bladder tumor (TURBT followed by intravesical chemotherapy is a conservative strategy for treatment of T1G3 bladder cancer, a relatively high risk of tumor recurrence and progression remains regarding the therapy. This study aimed to compare the efficacy of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder cancer after TURBT surgery. Methods: We retrospectively reviewed the cases of 457 patients who were newly diagnosed with T1G3 bladder urothelial carcinoma between January 2009 and March 2014. After TURBT, 281 patients received intravesical chemotherapy alone, whereas 176 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. Tumor recurrence and progression were monitored periodically by urine cytology and cystoscopy in follow-up. Recurrence-free survival and progression-free survival of the two chemotherapy strategies following TURBT were analyzed. Univariable and multivariable Cox hazards analyses were performed to predict the prognostic factors for tumor recurrence and progression. Results: The tumor recurrence rate was 36.7% for patients who received intravesical chemotherapy alone after TURBT, compared with 19.9% for patients who received intravenous chemotherapy combined with intravesical chemotherapy after

Treatment of lymphatic nodes metastasis in advanced cancer with interventional chemotherapy combined radiotherapy

International Nuclear Information System (INIS)

Xia Shian; Guo Weijian; Wu Guohua; Lin Qing; Jiang Mawei; Yao Yuan

2000-01-01

Objective: To evaluate the clinical effects of treatment with interventional chemotherapy combined radiotherapy for lymphatic nodes metastasis in advanced cancer. Methods: Treated with interventional chemotherapy for 27 cases of lymphatic rode metastasis once a month with average 2-3 times totally. Simultaneously treated with linear accelerator radiotherapy with average dose of 40-50 Gy/20-25 times/4-5 weeks. Results: To evaluate the clinical effects after finished the whole treatment program two months later. CR + PR reached 77.8% (24/27). All patients showed tolerance to accept the treatment. Conclusion: Treatment for lymphatic node metastasis in advanced cancer with interventional chemotherapy combined radiation therapy seems to be a valuable way

Early experience of proton beam therapy combined with chemotherapy for locally advanced oropharyngeal cancer

International Nuclear Information System (INIS)

Ishikawa, Youjirou; Nakamura, Tatsuya; Takada, Akinori; Takayama, Kanako; Makita, Chiyoko; Suzuki, Motohisa; Azami, Yusuke; Kikuchi, Yasuhiro; Fuwa, Nobukazu

2013-01-01

Between 2009 and 2012, 10 patients with advanced oropharyngeal cancer underwent proton therapy combined with chemotherapy. The initial results of this therapy were 8 complete response (CR) and 2 partial response (PR), local recurrence was detected 1 patient. Proton beam therapy combined with chemotherapy is thought to be an effective treatment for locally advanced oropharyngeal cancer. (author)

Treatment of non-Hodgkin lymphoma and mature В-cell acute leukemia in children and adolescents: data of Russian regional hospitals

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Ye. V. Samochatova

2014-07-01

Full Text Available The article presents treatment results of 233 patients (children and adolescents under 19 years old; median — 8.76 years with CD20-positive non-Hodgkin lymphomas and B-cell acute leukemia (B-NHL/B-AL received chemotherapy (BFM B-NHL 90–95 protocols or combined chemo-immunotherapy with rituximab (B-NHL-2004mab protocol. Combined chemo-immunotherapy was used for patients with Burkitt lymphoma, diffuse large cells lymphomas stage III–IV and B-AL, and included cytoreductive phase, 6 polychemotherapy (PCT courses and rituximab. PCT courses are similar to those of original BFM B-NHL90 protocol, except for the first 2 courses, where daily methotrexate dose was reduced from 5 to 1 g/m2/24 h. Rituximab infused IV 12 hours before the start of first 4 chemotherapy courses at a dose of 375 mg/m2. The data in the questionnaires form have been submitted from 28 pediatric specialized hospitals from 27 Russia regions over the past 5 years (2005–2009. Protocol with rituximab has proved to be more effective than chemotherapy alone. The authors discuss the possibility of using combined chemo-immunotherapy for the treatment of B-NHL/B-AL at regional hospitals and the prospects for further treatment results improvement in this group of tumors.

Treatment of non-Hodgkin lymphoma and mature В-cell acute leukemia in children and adolescents: data of Russian regional hospitals

Directory of Open Access Journals (Sweden)

Ye. V. Samochatova

2011-01-01

Full Text Available The article presents treatment results of 233 patients (children and adolescents under 19 years old; median — 8.76 years with CD20-positive non-Hodgkin lymphomas and B-cell acute leukemia (B-NHL/B-AL received chemotherapy (BFM B-NHL 90–95 protocols or combined chemo-immunotherapy with rituximab (B-NHL-2004mab protocol. Combined chemo-immunotherapy was used for patients with Burkitt lymphoma, diffuse large cells lymphomas stage III–IV and B-AL, and included cytoreductive phase, 6 polychemotherapy (PCT courses and rituximab. PCT courses are similar to those of original BFM B-NHL90 protocol, except for the first 2 courses, where daily methotrexate dose was reduced from 5 to 1 g/m2/24 h. Rituximab infused IV 12 hours before the start of first 4 chemotherapy courses at a dose of 375 mg/m2. The data in the questionnaires form have been submitted from 28 pediatric specialized hospitals from 27 Russia regions over the past 5 years (2005–2009. Protocol with rituximab has proved to be more effective than chemotherapy alone. The authors discuss the possibility of using combined chemo-immunotherapy for the treatment of B-NHL/B-AL at regional hospitals and the prospects for further treatment results improvement in this group of tumors.

Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event.

Science.gov (United States)

Berger, Joseph R; Malik, Vineeta; Lacey, Stuart; Brunetta, Paul; Lehane, Patricia B

2018-03-05

This report assesses the observed risk of PML in patients treated with the anti-CD20 monoclonal antibody rituximab in the regulatory authority-approved autoimmune indications rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). This was a cumulative analysis of confirmed PML cases in patients receiving rituximab for RA or GPA/MPA from both spontaneous reports and clinical trial sources, as captured in the manufacturer global company safety and clinical databases. Overall reporting rates were calculated and patient case details were summarized. As of 17 November 2015, there were nine confirmed PML cases among patients who had received rituximab for RA and two for GPA. Corresponding estimated reporting rates were 2.56 per 100,000 patients with RA (estimated exposure ≈ 351,396 patients) and < 1 per 10,000 patients with GPA/MPA (estimated exposure 40,000-50,000 patients). In all cases, patients had ≥ 1 potential risk factor for PML independent of rituximab treatment. In the RA population, the estimated reporting rate of PML generally remained stable and low since 2009 despite increasing rituximab exposure. There was no pattern of latency from time of rituximab initiation to PML development and no association of PML with the number of rituximab courses. Global post-marketing safety and clinical trial data demonstrated that the occurrence of PML is very rare among rituximab-treated patients with RA or GPA/MPA and has remained stable over time.

The identification of irreversible rituximab-resistant lymphoma caused by CD20 gene mutations

Energy Technology Data Exchange (ETDEWEB)

Mishima, Y [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Olympas Bio-Imaging Lab, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Terui, Y [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Takeuchi, K [Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo (Japan); Matsumoto-Mishima, Y; Matsusaka, S [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Utsubo-Kuniyoshi, R [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Olympas Bio-Imaging Lab, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan); Hatake, K [Department of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo (Japan)

2011-04-01

C-terminal mutations of CD20 constitute part of the mechanisms that resist rituximab therapy. Most CD20 having a C-terminal mutation was not recognized by L26 antibody. As the exact epitope of L26 has not been determined, expression and localization of mutated CD20 have not been completely elucidated. In this study, we revealed that the binding site of L26 monoclonal antibody is located in the C-terminal cytoplasmic region of CD20 molecule, which was often lost in mutated CD20 molecules. This indicates that it is difficult to distinguish the mutation of CD20 from under expression of the CD20 protein. To detect comprehensive CD20 molecules including the resistant mutants, we developed a novel monoclonal antibody that recognizes the N-terminal cytoplasm region of CD20 molecule. We screened L26-negative cases with our antibody and found several mutations. A rituximab-binding analysis using the cryopreserved specimen that mutation was identified in CD20 molecules indicated that the C-terminal region of CD20 undertakes a critical role in presentation of the large loop in which the rituximab-binding site locates. Thus, combination of antibodies of two kinds of epitope permits the identification of C-terminal CD20 mutations associated with irreversible resistance to rituximab and may help the decision of the treatment strategy.

Combined chemotherapy and radiation therapy in limited disease small-cell lung cancer

Energy Technology Data Exchange (ETDEWEB)

Kim, Moon Kyung; Ahn, Yong Chan; Park, Keun Chil; Lim Do Hoon; Huh, Seung Jae; Kim, Dae Yong; Shin, Kyung Hwan; Lee, Kyu Chan; Kwon, O Jung [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)

1999-03-01

This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer. Forty six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen (etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deliver 44 Gy using 10MV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylactic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved in 30 (65%) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50%), anemia in 17 (37%), thrombo-cytopenia in nine (20%), alopecia in nine (20%), nausea/vomiting in five (11%), and peripheral neuropathy in one (2%). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24%) out of the total 246 cycles. No radiation esophagitis over grade III was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The

Combined chemotherapy and radiation therapy in limited disease small-cell lung cancer

International Nuclear Information System (INIS)

Kim, Moon Kyung; Ahn, Yong Chan; Park, Keun Chil; Lim Do Hoon; Huh, Seung Jae; Kim, Dae Yong; Shin, Kyung Hwan; Lee, Kyu Chan; Kwon, O Jung

1999-01-01

This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer. Forty six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen (etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deliver 44 Gy using 10MV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylactic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved in 30 (65%) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50%), anemia in 17 (37%), thrombo-cytopenia in nine (20%), alopecia in nine (20%), nausea/vomiting in five (11%), and peripheral neuropathy in one (2%). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24%) out of the total 246 cycles. No radiation esophagitis over grade III was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The

Beneficial effect of tocilizumab in myasthenia gravis refractory to rituximab.

Science.gov (United States)

Jonsson, Dagur Ingi; Pirskanen, Ritva; Piehl, Fredrik

2017-06-01

Muscle fatigue associated with myasthenia gravis is caused by autoantibodies interfering with neuromuscular transmission. Immunomodulating treatment is widely used in moderate to severe myasthenia, although the use of newer biological drugs except rituximab is rare. We describe the effect of tocilizumab, a blocker of interleukin-6 signalling, in two female myasthenia patients with high titres of serum acetylcholine receptor antibodies and insufficient response to rituximab. The first patient had been treated with high dose immunoglobulins regularly for several years and the second patient had been treated both with different oral immune suppressants and immunoglobulins before testing a low dose of rituximab without significant clinical effect. Subsequent treatment with tocilizumab resulted in clinical improvement within a few months. The first patient was switched back to rituximab, which resulted in worsening until tocilizumab was restarted. Tocilizumab can be a therapeutic option in cases not responding to rituximab. Copyright © 2017 Elsevier B.V. All rights reserved.

Combining biological agents and chemotherapy in the treatment of cholangiocarcinoma

DEFF Research Database (Denmark)

Jensen, Lars Henrik; Jakobsen, Anders

2011-01-01

is not always possible. Chemotherapy is effective and the combination of cisplatin and gemcitabine is considered a standard treatment of inoperable cholangiocarcinoma. Biological targeted treatment to date has minor effect when given as monotherapy, but some of the drugs hold promise as an adjunct...... to chemotherapy. It should, however, be noted that most of the trials are based on few patients, and thus far the literature does not allow for a conclusion as to the role of biological treatment on cholangiocarcinoma. This situation calls for well-designed randomized trials, and international cooperation as well...

Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

DEFF Research Database (Denmark)

van Imhoff, Gustaaf W; McMillan, Andrew; Matasar, Matthew J

2017-01-01

Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Pat...

Evaluación económica de rituximab en combinación con fludarabina y ciclofosfamida en comparación con fludarabina y ciclofosfamida en el tratamiento de la leucemia linfática crónica Economic evaluation of rituximab added to fludarabine plus cyclophosphamide versus fludarabine plus cyclophosphamide for the treatment of chronic lymphocytic leukemia

Directory of Open Access Journals (Sweden)

Luis Felipe Casado

2011-08-01

Full Text Available Objetivos: Evaluar el coste-efectividad del esquema de rituximab, fludarabina y ciclofosfamida (R-FC en comparación con el de fludarabina y ciclofosfamida (FC en dos tipos de pacientes con leucemia linfática crónica (LLC: no tratados previamente o bien en recidiva/resistentes al tratamiento previo. Métodos: Dos modelos de Markov, utilizando los resultados publicados de superviviencia libre de progresión (SLP de pacientes con LLC tratados con R-FC o FC en primera o segunda línea, las tasas de progresión de la enfermedad y las tasas de mortalidad en España. A los estados de SLP y progresión se les asignaron utilidades obtenidas en un estudio sobre LLC. Los costes de los medicamentos y de los tratamientos de soporte, así como los años de vida ajustados por calidad (AVAC, se estimaron para un periodo de 10 años. Se efectuaron análisis de sensibilidad univariados y probabilísticos (Monte Carlo. Resultados: La adición de rituximab a la quimioterapia con FC aumentó los años de vida ganados (AVG y los AVAC tanto en primera como en segunda línea de tratamiento. La razón de coste-eficacia incremental fue de 20.703 € por AVG y de 19.343 € por AVAC con la primera línea de tratamiento, y de 23.183 € por AVG y 24.781 € por AVAC con la segunda línea de tratamiento. Conclusiones: En los pacientes con LLC no tratados previamente y en aquellos en recaída o resistentes al tratamiento previo, la adición de rituximab al esquema FC aumentó la esperanza de vida y los AVAC, y en ambos casos resultó ser un tratamiento coste-efectivo.Objectives: We evaluated the cost-effectiveness of rituximab added to the chemotherapy regimen of fludarabine plus cyclophosphamide (R-FC versus fludarabine plus cyclophosphamide (FC for the treatment of patients with previously untreated or relapsed/refractory chronic lymphocytic leukemia (CLL. Methods: Two Markov models were built, using published results on progression-free survival (PFS in patients

Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy.

Science.gov (United States)

Dogra, Mohit; Bajgai, Priya; Kumar, Ashok; Sharma, Aman

2018-04-01

We report a case of progressive outer retinal necrosis (PORN) in a patient of microscopic polyangitis (MPA), being treated with immunosuppressive drugs such as cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster virus and she was treated with oral and intravitreal antivirals, along with discontinuation of one of the immunosuppressive agents, i.e. rituximab, which might have led to reactivation of the virus causing necrotizing retinitis lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are necessary to manage immunological disorders such as MPA. However, they may predispose the patient to serious complications like viral infections, including PORN.

Rituximab in anti-GBM disease: A retrospective study of 8 patients.

Science.gov (United States)

Touzot, Maxime; Poisson, Johanne; Faguer, Stanislas; Ribes, David; Cohen, Pascal; Geffray, Loic; Anguel, Nadia; François, Helene; Karras, Alexandre; Cacoub, Patrice; Durrbach, Antoine; Saadoun, David

2015-06-01

Anti-glomerular basement membrane (GBM) disease is a rare autoantibody-mediated disorder presenting as rapidly progressive glomerulonephritis, and often with pulmonary hemorrhage. Antibody removal with plasmapheresis and immunosuppressive drugs are the cornerstones of the treatment. Data regarding the use of specific B-cell depleting therapy such as rituximab are lacking. We conducted a retrospective observational study of 8 patients with severe and/or refractory GBM disease that received rituximab therapy. Eight patients (2 men, 6 women) with a mean age of 26 ± 13.1 years old were included. Seven had severe renal involvement [median creatinin level was 282 μmol/l, range (65-423)] requiring high immunosuppressive or plasmapheresis dependent, and two had relapse of pulmonary hemorrhage including one with renal failure. Patients received an initial immunosuppressive treatment including steroid and cyclosphosphamide (n = 8) and plasmapheresis (n = 5). Except one late relapse, rituximab therapy was started within two months after diagnosis. All patients except one received 4 weekly dose of rituximab (375 mg(2)). Anti-GBM antibodies were still present in 6/8 patients, at rituximab initiation. Complete remission was observed in 7 out of 8 patients, mostly 3 months after rituximab therapy. After a mean follow-up of 25.6 months (range 4-93), patient and renal survival were 100% and 75% respectively, but rituximab use did not improve GFR. Anti-GBM antibodies remained negative for all patients during follow-up. Only one patient developed a severe bacterial infection but no opportunistic or viral infections were reported. Rituximab may represent an additional and/or alternative therapy in the induction treatment of anti-GBM disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

SEROTONIN METABOLISM FOLLOWING PLATINUM-BASED CHEMOTHERAPY COMBINED WITH THE SEROTONIN TYPE-3 ANTAGONIST TROPISETRON

NARCIS (Netherlands)

SCHRODER, CP; VANDERGRAAF, WTA; KEMA, IP; GROENEWEGEN, A; SLEIJFER, DT; DEVRIES, EGE

1995-01-01

The administration of platinum-based chemotherapy induces serotonin release from the enterochromaffin cells, causing nausea and vomiting. This study was conducted to evaluate parameters of serotonin metabolism following platinum-based chemotherapy given in combination with the serotonin type-3

Effect of Hyperthermic Intraperitoneal Perfusion Chemotherapy in Combination with Intravenous Chemotherapy as Postoperative Adjuvant Therapy for Advanced Gastric Cancer.

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Wu, Zhibing; Ma, Shenglin; Jing, Saisai; Deng, Qinghua; Zheng, Zhishuang; Wu, Kan; Li, Juan; Chen, Sumei; Tang, Rongjun; Li, Xiadong

2014-06-01

The aim is to evaluate the preliminary efficacy and side effects of paclitaxel, 5-fluorouracil, and leucovorin intravenous chemotherapy in combination with cisplatin hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) as postoperative adjuvant therapy for patients of locally advanced gastric cancer (GC) at high risk for recurrence after curative resection. Four GC patients who underwent radical gastrectomy with D2 lymphadenectomy were enrolled. All patients received paclitaxel 135 mg/m2 on day 1, 5-FU 500 mg/m2 on days 1-5, LV 200 mg/m2 on days 1-5 intravenous chemotherapy, cisplatin 75 mg/m2 on day 5, and HIPEC one month after surgery. It was repeated at 3 weeks intervals and at least two cycles administered. A total of 181 cycles of chemotherapy were administered (median, 4 cycles). The median disease free survival time of patients was 40.8 months. The median overall survival time was 48.0 months. The one-, two-, and three-year recurrence rates were 14.6%, 26.8%, and 46.3%, respectively. The main relapse patterns were remnant GC and metastases of retroperitoneal lymph nodes. The morbidity of grade 3 and 4 toxicities of myelosuppression, nausea/ vomiting were less than 10%. The side effects of grade 1 and 2 of hematologic toxicity, nausea and vomiting, abnormal function of liver, kidney or cardiac, fatigue and neurotoxicity were well tolerated. Cisplatin HIPEC combined with paclitaxel, 5-fluorouracil, and leucovorin intravenous chemotherapy regimen could improve the survival rate and decrease the postoperative recurrence of locally advanced GC.

Impact of the use of autologous stem cell transplantation at first relapse both in naïve and previously rituximab exposed follicular lymphoma patients treated in the GELA/GOELAMS FL2000 study

Science.gov (United States)

Le Gouill, Steven; De Guibert, Sophie; Planche, Lucie; Brice, Pauline; Dupuis, Jehan; Cartron, Guillaume; Van Hoof, Achiel; Casasnovas, Olivier; Gyan, Emmanuel; Tilly, Hervé; Fruchart, Christophe; Deconinck, Eric; Fitoussi, Olivier; Gastaud, Lauris; Delwail, Vincent; Gabarre, Jean; Gressin, Rémy; Blanc, Michel; Foussard, Charles; Salles, Gilles

2011-01-01

Background We analyzed detailed characteristics and salvage treatment in 175 follicular lymphoma patients from the FL2000 study who were in progression after first-line therapy with or without addition of rituximab to chemotherapy and interferon. Design and Methods The impact of using autologous stem cell transplantation and/or rituximab administration at first progression was investigated, taking into account initial therapy. With a median follow up of 31 months, 3-year event free and overall survival rates after progression were 50% (95%CI 42–58%) and 72% (95%CI 64–78%), respectively. Results The 3-year event free rate of rituximab re-treated patients (n=112) was 52% (95%CI 41–62%) versus 40% (95%CI 24–55%) for those not receiving rituximab second line (n=53) (P=0.075). There was a significant difference in 3-year overall survival between patients receiving autologous stem cell transplantation and those not: 92% (95%CI 78–97%) versus 63% (95%CI 51–72%) (P=0.0003), respectively. In multivariate analysis, both autologous stem cell transplantation and period of progression/relapse affected event free and overall survival. Conclusions Regardless of front-line rituximab exposure, this study supports incorporating autologous stem cell transplantation in the therapeutic approach at first relapse for follicular lymphoma patients. PMID:21486862

Chemotherapy and molecular target therapy combined with radiation therapy

International Nuclear Information System (INIS)

Akimoto, Tetsuo

2012-01-01

Combined chemotherapy and radiation therapy has been established as standard treatment approach for locally advanced head and neck cancer, esophageal cancer and so on through randomized clinical trials. However, radiation-related morbidity such as acute toxicity also increased as treatment intensity has increased. In underlining mechanism for enhancement of normal tissue reaction in chemo-radiation therapy, chemotherapy enhanced radiosensitivity of normal tissues in addition to cancer cells. Molecular target-based drugs combined with radiation therapy have been expected as promising approach that makes it possible to achieve cancer-specific enhancement of radiosensitivity, and clinical trials using combined modalities have been performed to evaluate the feasibility and efficacy of this approach. In order to obtain maximum radiotherapeutic gain, a detailed understanding of the mechanism underlying the interaction between radiation and Molecular target-based drugs is indispensable. Among molecular target-based drugs, inhibitors targeting epidermal growth factor receptor (EGFR) and its signal transduction pathways have been vigorously investigated, and mechanisms regarding the radiosensitizing effect have been getting clear. In addition, the results of randomized clinical trials demonstrated that radiation therapy combined with cetuximab resulted in improvement of overall and disease-specific survival rate compared with radiation therapy in locally advanced head and neck cancer. In this review, clinical usefulness of chemo-radiation therapy and potential molecular targets for potentiation of radiation-induced cell killing are summarized. (author)

Effects of multidose combination chemotherapy on the humoral immune system

NARCIS (Netherlands)

Zandvoort, A; Lodewijk, ME; Klok, PA; Timens, W

Patients receiving multidose combination chemotherapy are at risk for severe, life-threatening infections, caused by among others encapsulated bacteria like Streptococcus pneumoniae. The splenic marginal zone is essential in the initiation of immune responses to S. pneumoniae. We analyzed effects of

Comparing Intra-Arterial Chemotherapy Combined With Intravesical Chemotherapy Versus Intravesical Chemotherapy Alone: A Randomised Prospective Pilot Study for T1G3 Bladder Transitional Cell Carcinoma After Bladder-Preserving Surgery

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Chen, Junxing, E-mail: Junxingchen@hotmail.com; Yao, Zhijun, E-mail: yaozhijun1985@qq.com; Qiu, Shaopeng, E-mail: qiushp@mail.sysu.edu.cn; Chen, Lingwu, E-mail: chenlingwu@hotmail.com [First Affiliated Hospital of Sun Yat-Sen University, Department of Urology (China); Wang, Yu, E-mail: zsyyjr@163.com; Yang, Jianyong, E-mail: yangjianyong_2011@163.com; Li, Jiaping, E-mail: jpli3s@126.com [First Affiliated Hospital of Sun Yat-Sen University, Department of Interventional Oncology (China)

2013-12-15

Purpose: To compare the efficacy of intra-arterial chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder transitional cell carcinoma (BTCC) followed by bladder-preserving surgery. Materials and Methods: Sixty patients with T1G3 BTCC were randomly divided into two groups. After bladder-preserving surgery, 29 patients (age 30-80 years, 24 male and 5 female) received intra-arterial chemotherapy in combination with intravesical chemotherapy (group A), whereas 31 patients (age 29-83 years, 26 male and 5 female) were treated with intravesical chemotherapy alone (group B). Twenty-nine patients were treated with intra-arterial epirubicin (50 mg/m{sup 2}) + cisplatin (60 mg/m{sup 2}) chemotherapy 2-3 weeks after bladder-preserving surgery once every 4-6 weeks. All of the patients received the same intravesical chemotherapy: An immediate prophylactic was administered in the first 6 h. After that, therapy was administered one time per week for 8 weeks and then one time per month for 8 months. The instillation drug was epirubicin (50 mg/m{sup 2}) and lasted for 30-40 min each time. The end points were tumour recurrence (stage Ta, T1), tumour progression (to T2 or greater), and disease-specific survival. During median follow-up of 22 months, the overall survival rate, tumour-specific death rate, recurrence rate, progression rate, time to first recurrence, and adverse reactions were compared between groups. Results: The recurrence rates were 10.3 % (3 of 29) in group A and 45.2 % (14 of 31) in group B, and the progression rates were 0 % (0 of 29) in group A and 22.6 % (7 of 31) in group B. There was a significant difference between the two groups regarding recurrence (p = 0.004) and progression rates (p = 0.011). Median times to first recurrence in the two groups were 15 and 6.5 months, respectively. The overall survival rates were 96.6 and 87.1 %, and the tumour-specific death rates were 0 % (0 of 29) and 13.5 % (4 of 31

Parvovirus B19 reactivation presenting as neutropenia after rituximab treatment.

Science.gov (United States)

Klepfish, A; Rachmilevitch, E; Schattner, A

2006-11-01

A patient with primary biliary cirrhosis and associated refractory immune thrombocytopenic purpura was treated with 4 weekly courses of rituximab, a monoclonal antibody targeting B-cell surface antigen CD20. Her thrombocyte count and even cholestatic liver function tests improved. However, 17 weeks after rituximab treatment, she developed severe neutropenia (absolute neutrophil count 0.23x10(3)/mul) and recurrent thrombocytopenia with abnormal bone marrow of all three lineages. Although delayed-onset neutropenia has been reported after rituximab, reactivated viral infections have also been encountered. Parvovirus B19 was suspected and confirmed as the cause of neutropenia in our patient. The patient was supported by GCSF treatment and recovered uneventfully after several weeks. Neutropenia after rituximab can also be the predominant manifestation of reactivated parvovirus B19 infection and have a favorable prognosis.

Induction chemotherapy for locoregional lung cancer using paclitaxel combination. A preliminary report

International Nuclear Information System (INIS)

Takita, H.; Pitoniak, R.F.

2000-01-01

Induction chemotherapy has been reported to be effective in treatment of locally advanced, borderline resectable, (Stage III), non small cell lung carcinoma (NSCLC). A logical extension of the indication for the induction chemotherapy may be to treat earlier stage resectable lung cancers (stages I and II) because the cure rate of the resectable lung cancers still remains poor and is below 60% except for stage I A. Thirty eight patients with a diagnosis of loco-regional NSCLC were treated with paclitaxel combination chemotherapy. Following two courses of induction chemotherapy, patients underwent surgical therapy whenever possible. There ten patients with stage I disease, four patients with stage II, 13 with stage IIIA, nine had stage IIIB, and two with stage IV. An overall response rate of 74% was observed. The response rate for 14 resectable patients (stage I and II) was 86%. The chemotherapy regimen was well tolerated and apart from one instance of anaphylaxis, no serious side effects were observed

High-dose chemotherapy and immunotherapy in adult Burkitt lymphoma: comparison of results in human immunodeficiency virus-infected and noninfected patients.

Science.gov (United States)

Oriol, Albert; Ribera, Josep-Maria; Bergua, Juan; Giménez Mesa, Eduardo; Grande, Carlos; Esteve, Jordi; Brunet, Salut; Moreno, Maria-Jose; Escoda, Lourdes; Hernandez-Rivas, Jesus-Maria; Hoelzer, Dieter

2008-07-01

It has been recognized that cure is possible for human immunodeficiency virus (HIV)-infected patients with Burkitt lymphoma/leukemia (BL) if appropriate chemotherapy is used. The introduction of rituximab in BL therapeutic schemes has been scarcely explored. The outcome and toxicity of HIV-positive patients with BL treated in a rituximab and intensive chemotherapy-based trial was evaluated. Thirty-six consecutive patients, 15 to 55 years of age, diagnosed with advanced stage BL were recruited from July 2003 to August 2006, stratified according to HIV infection status and treated with 6 cycles of intensive chemotherapy including 8 doses of rituximab. Nineteen of the patients (53%) were HIV-infected. Their clinical characteristics were comparable to those of the HIV-negative patients. Complete remission (CR) rates were 88% and 84%, respectively, for HIV-negative and -positive patients. Twenty-seven patients (82% and 68%, respectively, for HIV-negative and -positive patients) completed the 6 protocol scheduled cycles. HIV-infected patients presented higher incidences of grade 3-4 mucositis (27% vs 7% of cycles, P = .0005) and severe infectious episodes (26% vs 8%, P = .0025). However, there were no statistically significant differences in 2-year overall survival (82%, 95% confidence interval [CI], 65%-99% and 73%, 95% CI, 54%-92%, respectively) or 2-year disease-free survival (93%, 95% CI, 82%-99% and 87%, 95% CI 72%-99%, respectively). Intensive immunochemotherapy can be administered safely to patients with HIV infection. Despite a higher incidence of severe mucositis and infections the remission and survival rates are comparable to those observed in HIV-negative patients. (Copyright) 2008 American Cancer Society.

Intermediate doses of rituximab used as adjuvant therapy in refractory pemphigus

Directory of Open Access Journals (Sweden)

Pradnya J Londhe

2014-01-01

Full Text Available Background: Rituximab, a monoclonal anti-CD20 antibody, has been used with encouraging results in pemphigus. We describe herein refractory cases of pemphigus vulgaris (n = 23 and pemphigus foliaceus (n = 1 treated with rituximab in addition to steroids and immunosuppressants. Aims: To assess the response to treatment, the duration of clinical remission, serology of the response and adverse effects of rituximab in pemphigus patients. Methods: We recorded observations of 24 patients with pemphigus having either refractory disease in spite of high dose of steroids and immunosuppressants, corticosteroid-dependent disease, strong contraindications to corticosteroids, or severe disease. The patients were treated with infusions of one injection per week for three consecutive weeks of 375 mg of rituximab per m 2 of body-surface area. One similar infusion was repeated after 3 months of 3 rd dose. We observed the clinical outcome after 6 months of 3 rd dose of rituximab and looked for complete healing of cutaneous and mucosal lesions (complete remission. Observations: After follow-up of 7-24 months, five patients showed only partial improvement while 19 of 24 patients had a complete remission 3 months after rituximab. Of these 19 patients, 12 patients achieved complete remission and are off all systemic therapy, and the rest are continuing with no or low dose of steroids with immunosuppressants. Two patients relapsed after initial improvement; one was given moderate dose of oral steroids and immunosuppressant and the other was given repeat single dose of rituximab to control relapse. Conclusion: Rituximab is able to induce a prolonged clinical remission in pemphigus after a single course of four infusions. The high cost and limited knowledge of long term adverse effects are limitations to the use of this biologic agent.

Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy

Directory of Open Access Journals (Sweden)

Mohit Dogra

2018-01-01

Full Text Available We report a case of progressive outer retinal necrosis (PORN in a patient of microscopic polyangitis (MPA, being treated with immunosuppressive drugs such as cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster virus and she was treated with oral and intravitreal antivirals, along with discontinuation of one of the immunosuppressive agents, i.e. rituximab, which might have led to reactivation of the virus causing necrotizing retinitis lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are necessary to manage immunological disorders such as MPA. However, they may predispose the patient to serious complications like viral infections, including PORN.

Combination cancer chemotherapy with one compound: pluripotent bradykinin antagonists.

Science.gov (United States)

Stewart, John M; Gera, Lajos; Chan, Daniel C; York, Eunice J; Simkeviciene, Vitalija; Bunn, Paul A; Taraseviciene-Stewart, Laimute

2005-08-01

Lung and prostate cancers are major health problems worldwide. Treatments with standard chemotherapy agents are relatively ineffective. Combination chemotherapy gives better treatment than a single agent because the drugs can inhibit the cancer in different pathways, but new therapeutic agents are needed for the treatment of both tumor types. Bradykinin (BK) antagonists offer advantages of combination therapy in one compound. These promising multitargeted anti-cancer compounds selectively stimulate apoptosis in cancers and also inhibit both angiogenesis and matrix metalloprotease (MMP) action in treated lung and prostate tumors in nude mice. The highly potent, metabolism-resistant bradykinin antagonist peptide dimer, B-9870 [SUIM-(DArg-Arg-Pro-Hyp-Gly-Igl-Ser-DIgl-Oic-Arg)2] (SUIM=suberimidyl; Hyp=4-hydroxyproline; Igl=alpha-(2-indanyl)glycine; Oic=octahydroindole-2-carboxylic acid) and its non-peptide mimetic, BKM-570 [2,3,4,5,6-pentafluorocinnamoyl-(o-2,6-dichlorobenzyl)-L-tyrosine-N-(4-amino-2,2,6,6-tetramethylpiperidyl)amide] are superior to the widely used but toxic chemotherapeutic drugs cisplatin and taxotere. In certain combinations, they act synergistically with standard anti-cancer drugs. Due to its structure and biological activity, BKM-570 is an attractive lead compound for derivatization and evaluation for lung and prostate cancer drugs.

Relapse of nephrotic syndrome during post-rituximab peripheral blood B-lymphocyte depletion.

Science.gov (United States)

Sato, Mai; Kamei, Koichi; Ogura, Masao; Ishikura, Kenji; Ito, Shuichi

2018-02-01

Rituximab is effective against complicated childhood steroid-dependent nephrotic syndrome (SDNS). Peripheral blood B-lymphocyte (B-cell) depletion is strongly correlated with persistent remission, relapse rarely occurring during B-cell depletion; however, we have encountered several such patients. We retrospectively analyzed the characteristics and clinical course of 82 patients with SDNS treated with rituximab from January 2007 to December 2012 in our institution. Six of 82 patients (7.3%) had relapses during B-cell depletion after receiving rituximab (relapsed group). The remaining 76 patients did not have relapses during B-cell depletion (non-relapsed group). The median time to initial relapse during B-cell depletion was 85 days after receiving rituximab, which is significantly shorter than in the non-relapsed group (410 days, p = 0.0003). The median annual numbers of relapses after receiving rituximab were 2.5 and 0.9 in the relapsed and non-relapsed groups, respectively (p depletion did not differ between the two groups. Relapse during B-cell depletion after receiving rituximab suggests that various pathophysiological mechanisms play a part in childhood nephrotic syndrome.

[Efficacy of MVP chemotherapy combined with concurrent radiotherapy for advanced non-small cell lung cancer].

Science.gov (United States)

Qiao, Tiankui; Zhou, Daoan; Chen, Wei; Wang, Xianglian

2004-12-20

To observe the effects of MVP chemotherapy combined with concurrent radiotherapy for stage IIIB-IV non-small cell lung cancer. Sixty-two patients with stage IIIB-IV non-small cell lung cancer were randomized into two groups, concurrent radiochemotherapy group and MVP che-motherapy group. All patients in two groups were treated with MVP regimen (mitomycin C 6 mg/m² on day 1, vindesine 2 mg/m² on days 1, 8, and cisplatin 80-100 mg/m²). Patients in concurrent radiochemotherapy group received concurrent radiotherapy (46-56 Gy in 5-6 weeks). All patients received 2-4 cycles of MVP chemotherapy. The response rate was 48.4% and 19.4% in concurrent radiochemotherapy group and MVP group respectively (P MVP group.. The results show that efficacy of MVP chemotherapy combined with concurrent radiotherapy is significantly higher than that of MVP chemotherapy alone for advanced non-small cell lung cancer.

Kinetics of Rituximab Excretion into Urine and Peritoneal Fluid in Two Patients with Nephrotic Syndrome.

Science.gov (United States)

Stahl, Klaus; Duong, Michelle; Schwarz, Anke; Wagner, A D; Haller, Hermann; Schiffer, Mario; Jacobs, Roland

2017-01-01

Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty's syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.

Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance.

Science.gov (United States)

Khdair, Ayman; Chen, Di; Patil, Yogesh; Ma, Linan; Dou, Q Ping; Shekhar, Malathy P V; Panyam, Jayanth

2010-01-25

Tumor drug resistance significantly limits the success of chemotherapy in the clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of anticancer drugs at their intracellular site of action. In this study, we investigated the anticancer efficacy of doxorubicin in combination with photodynamic therapy using methylene blue in a drug-resistant mouse tumor model. Surfactant-polymer hybrid nanoparticles formulated using an anionic surfactant, Aerosol-OT (AOT), and a naturally occurring polysaccharide polymer, sodium alginate, were used for synchronized delivery of the two drugs. Balb/c mice bearing syngeneic JC tumors (mammary adenocarcinoma) were used as a drug-resistant tumor model. Nanoparticle-mediated combination therapy significantly inhibited tumor growth and improved animal survival. Nanoparticle-mediated combination treatment resulted in enhanced tumor accumulation of both doxorubicin and methylene blue, significant inhibition of tumor cell proliferation, and increased induction of apoptosis. These data suggest that nanoparticle-mediated combination chemotherapy and photodynamic therapy using doxorubicin and methylene blue has significant therapeutic potential against drug-resistant tumors. Copyright 2009 Elsevier B.V. All rights reserved.

Molecular mechanisms of resistance to Rituximab and pharmacologic strategies for its circumvention.

Science.gov (United States)

Stolz, Claudia; Schuler, Martin

2009-06-01

The introduction of Rituximab has greatly improved therapeutic options for patients with B-cell non-Hodgkin lymphoma (B-NHL). However, a substantial fraction of patients with aggressive B-NHL fails first-line therapy, and most patients with relapsing indolent B-NHL eventually acquire Rituximab resistance. Molecular understanding of the underlying mechanisms facilitates the development of pharmacologic strategies to overcome resistance. Rituximab exerts its activity on CD20-expressing B-cells by indirect and direct effector mechanisms. Indirect mechanisms are complement-dependent cytotoxicity (CDC), and antibody-dependent cell-mediated cytotoxicity (ADCC). Direct activities, such as growth inhibition, induction of apoptosis and chemosensitisation, have been reported, but are less defined. Moreover, the relative contribution of CDC, ADCC and direct mechanisms to the activity of Rituximab in vivo is unclear. Down-regulation of CD20 and expression of complement inhibitors have been described as escape mechanisms in B-NHL. Recent reports suggest that deregulated phosphoinositide-3-kinase (PI3K)/Akt, mitogen-activated kinases (MAPK) and nuclear-factor kappaB (NF-kappaB), as well as up-regulation of anti-apoptotic proteins may determine the efficacy of Rituximab to kill B-NHL cells in vitro and in vivo. The latter signalling pathways are attractive targets for pharmacologic modulation of resistance to Rituximab. With the advent of new inhibitors and antibodies, rationally designed clinical trials addressing Rituximab resistance are feasible.

Neurophysiological and clinical responses to rituximab in patients with anti-MAG polyneuropathy.

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Zara, Gabriella; Zambello, Renato; Ermani, M

2011-12-01

Rituximab treatment has shown clinical improvement in anti-myelin associated glycoprotein (MAG) polyneuropathy. We analyzed scores of clinical scales and the most sensitive electrophysiological parameters before and after immunomodulating treatment with rituximab in a group of patients affected by anti-MAG demyelinating polyneuropathy. Clinical scores, the percentage of CD20 B-lymphocytes, anti-MAG antibody titers and electrophysiological data in 7 patients with anti-MAG polyneuropathy were analyzed. The patients were examined before a cycle with rituximab, 6, 12 and 24 months after the end of the treatment. Two patients were treated with rituximab additional cycles and re-evaluated 48 months after the first treatment. There were no evident correlation between anti-MAG serum antibody titers or clinical scales and electrodiagnostic data. Significant decrease in the proportion of CD20 B-lymphocytes was observed. Significant anti-MAG antibodies titers reduction was detected after re-treatment. At follow-up, pinprik sensation and two point discrimination presented a significant improvement compared with the score before treatment. In our patients, rituximab did not improve any electrophysiological data. No correlation with anti-MAG serum antibodies course was found. With rituximab only pin sensibility improved. Rituximab re-treatment significantly reduces anti-MAG serum antibodies titers but improves only small fibers sensibility. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Eficiency of different doses of rituximab in rheumatoid arthritis.

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Mena-Vázquez, Natalia; Manrique-Arija, Sara; Ureña-Garnica, Inmaculada; Romero-Barco, Carmen M; Jiménez-Núñez, Francisco G; Coret, Virginia; Irigoyen-Oyarzábal, María Victoria; Fernández-Nebro, Antonio

2016-01-01

Evaluate the effectiveness, cost and safety of rituximab in patients with rheumatoid arthritis (RA) depending on the dose used. Retrospective observational study conducted on 52 patients with RA treated with at least one dose of rituximab for 135.3 patient-years were included. Three treatment groups were obtained: (G1) First course and following two 1g infusions separated by 15 days; (G2) First course 2 infusions of 1g followed by 2 infusions of 500mg; (G3) First course and followed by 2 infusions of 500mg separated by 15 days. Re-treatments were administered on-demand according to the clinical activity. The retention time (Log-Rank), retreats and adverse events rates (incidence rate ratio) and treatment costs per patient-month of rituximab were analysed by groups. Group 2 showed a better cost-effectiveness ratio than group 1, as it was associated with a longer retention of rituximab (mean [95% CI] 65.7 [60.8 to 70.7] months vs 33.5 [22.7 to 44.3]; P<.001) and a lower rate of severe adverse events with only a slight increase in the rate of retreatment (courses/patient-year [95% CI] 1.66 [1.39 to 1.93] vs. 1.01 [0.69 to 1.34]; P=.005), and in the costs (median/patient-month, €484.89 vs. €473.45). Although group 3 was €41.20/patient-month cheaper than group 2, it was associated with a higher rate of re-treatments and shorter retention of rituximab (P<.001). The use of full-dose rituximab at onset, followed by reduced doses in successive courses administered on-demand retreatment may be the most cost-effective option. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Medical resource utilization in dermatomyositis/polymyositis patients treated with repository corticotropin injection, intravenous immunoglobulin, and/or rituximab

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Knight T

2017-05-01

Full Text Available Tyler Knight,1 T Christopher Bond,1 Breanna Popelar,2 Li Wang,3 John W Niewoehner,4 Kathryn Anastassopoulos,1 Michael Philbin4 1Covance Market Access Services Inc., Gaithersburg, MD, 2Xcenda, LLC, Palm Harbor, FL, 3STATinMED Research, Ann Arbor, MI, 4Mallinckrodt, LLC, Hazelwood, MO, USA Background: Dermatomyositis and polymyositis (DM/PM are rare, incurable inflammatory diseases that cause progressive muscle weakness and can be associated with increased medical resource use (MRU. When corticosteroid treatment is unsuccessful, patients may receive intravenous immunoglobulin (IVIg, rituximab, or repository corticotropin injection (RCI. This study compared real-world, non-medication MRU between patients treated with RCI and those treated with IVIg and/or rituximab for DM/PM.Methods: Claims of DM/PM patients were analyzed from the combination of three commercial health insurance databases in the United States from July 2009 to June 2014. Patients treated with RCI were propensity score matched to those treated with IVIg, rituximab, and both (IVIg+rituximab based on demographics, prior clinical characteristics, and prior MRU. Per-patient per-month (PPPM MRU and costs were compared using Poisson regression and generalized linear modeling, respectively.Results: One-hundred thirty-two RCI, 1,150 IVIg, and 562 rituximab patients had an average age of 52.6, 46.6, and 51.7 years, respectively, and roughly two-thirds were female. After matching, there were no significant differences in demographics or prior clinical characteristics. RCI patients had fewer PPPM hospitalizations (0.09 vs 0.17; P=0.049, shorter length of stay (LOS; 3.24 days vs 4.55 days; P=0.004, PPPM hospital outpatient department (HOPD visits (0.60 vs 1.39; P<0.001, and PPPM physician office visits (2.01 vs 2.33; P=0.035 than IVIg. RCI had fewer PPPM HOPD visits (0.56 vs 0.92; P<0.001 than rituximab. Patients treated with RCI had shorter LOS (2.18 days vs 5.15; P<0.001 and less PPPM HOPD

High treatment efficacy by dual targeting of Burkitt's lymphoma xenografted mice with a {sup 177}Lu-based CD22-specific radioimmunoconjugate and rituximab

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Weber, Tobias; Boetticher, Benedikt; Keller, Armin; Schlegelmilch, Anne; Jaeger, Dirk; Krauss, Juergen [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); Mier, Walter; Kraemer, Susanne; Leotta, Karin [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Sauter, Max; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Grosse-Hovest, Ludger [University of Tuebingen, Department of Immunology, Tuebingen (Germany); Arndt, Michaela A.E. [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); German Cancer Research Center (DKFZ), Immunotherapy Program, National Center for Tumor Diseases, Heidelberg (Germany)

2016-03-15

Dual-targeted therapy has been shown to be a promising treatment option in recurrent and/or refractory B-cell non-Hodgkin's lymphoma (B-NHL). We generated radioimmunoconjugates (RICs) comprising either a novel humanized anti-CD22 monoclonal antibody, huRFB4, or rituximab, and the low-energy β-emitter {sup 177}Lu. Both RICs were evaluated as single agents in a human Burkitt's lymphoma xenograft mouse model. To increase the therapeutic efficacy of the anti-CD22 RIC, combination therapy with unlabelled anti-CD20 rituximab was explored. The binding activity of CHX-A''-DTPA-conjugated antibodies to target cells was analysed by flow cytometry. To assess tumour targeting of {sup 177}Lu-labelled antibodies, in vivo biodistribution experiments were performed. For radioimmunotherapy (RIT) studies, non-obese diabetic recombination activating gene-1 (NOD-Rag1{sup null}) interleukin-2 receptor common gamma chain (IL2r γ {sup null}) null mice (NRG mice) were xenografted subcutaneously with Raji Burkitt's lymphoma cells. {sup 177}Lu-conjugated antibodies were administered at a single dose of 9.5 MBq per mouse. For dual-targeted therapy, rituximab was injected at weekly intervals (0.5 - 1.0 mg). Tumour accumulation of RICs was monitored by planar scintigraphy. Conjugation of CHX-A''-DTPA resulted in highly stable RICs with excellent antigen-binding properties. Biodistribution experiments revealed higher tumour uptake of the {sup 177}Lu-labelled anti-CD22 IgG than of {sup 177}Lu-labelled rituximab. Treatment with {sup 177}Lu-conjugated huRFB4 resulted in increased tumour growth inhibition and significantly longer survival than treatment with {sup 177}Lu-conjugated rituximab. The therapeutic efficacy of the anti-CD22 RIC could be markedly enhanced by combination with unlabelled rituximab. These findings suggest that dual targeting with {sup 177}Lu-based CD22-specific RIT in combination with rituximab is a promising new treatment option for

Kinetics of Rituximab Excretion into Urine and Peritoneal Fluid in Two Patients with Nephrotic Syndrome

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Klaus Stahl

2017-01-01

Full Text Available Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty’s syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.

Prolonged Remission in Neuromyelitis Optica Following Cessation of Rituximab Treatment.

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Weinfurtner, Kelley; Graves, Jennifer; Ness, Jayne; Krupp, Lauren; Milazzo, Maria; Waubant, Emmanuelle

2015-09-01

Neuromyelitis optica is an autoimmune disease characterized by acute episodes of transverse myelitis and optic neuritis. Several small, open-label studies suggest rituximab, a monoclonal antibody against CD20, prevents relapses in neuromyelitis optica; however, there is little consensus on timing or duration of treatment. Here we report four patients with severe relapsing neuromyelitis optica who were stabilized on rituximab and, after discontinuing treatment, continued to experience prolonged remission of their disease. Remission ranged from 4.5 to 10.5 years total, including 3 to 9 years off all therapies. The patients had sustained clinical responses despite normal B-lymphocyte levels and, in at least 2 patients, continued seropositivity for aquaporin-4 antibodies. These cases suggest that rituximab may induce prolonged remission in certain neuromyelitis optica patients, and they highlight the need for further elucidation of rituximab's mechanism in neuromyelitis optica. © The Author(s) 2014.

[Combination Chemotherapy Including Intraperitoneal(IP)Administration of Paclitaxel(PTX)followed by PTX, CDDP and S-1Triplet Chemotherapy for CY1P0 Gastric Cancer].

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Shinkai, Masayuki; Imano, Motohiro; Hiraki, Yoko; Kato, Hiroaki; Iwama, Mitsuru; Shiraishi, Osamu; Yasuda, Atsushi; Kimura, Yutaka; Imamoto, Haruhiko; Furukawa, Hiroshi; Yasuda, Takushi

2017-11-01

We evaluate the feasibility and efficacy of combination chemotherapy including single intraperitoneal( IP)administration of paclitaxel(PTX), followed by triplet chemotherapy(PTX, cisplatin[CDDP]and S-1: PCS)for CY1P0 gastric cancer. First of all, we performed staging laparoscopy and confirmed CY1P0, and secondary, administrated PTX intraperitoneally. Thirdly, patients received PCS chemotherapy for 2 courses. After antitumor effect had been confirmed, we performed second look laparoscopy. In the case of CY0P0, we performed gastrectomy with D2 lymph nodes dissection. Total 4 patients were enrolled. Grade 3 leukopenia and neutropenia were observed in one patient while intraperitoneal and systemic-chemotherapy. One patients showed PR and 3 patients showed SD. All patients underwent second look laparoscopy. CY0P0 was observed in all patients and gastrectomy with D2 dissection was performed for all patients. Postoperative complications were observed in 2 patients. Two patients were still alive without recurrence, while the remaining 2 had died of liver metastasis and #16 LN metastasis. Combination chemotherapy including single IP PTX followed by PCS systemic-chemotherapy for CY1P0 gastric cancer is feasible and efficient.

Treatment options for ocular adnexal lymphoma (OAL

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Victoria Mary Lendrum Cohen

2009-11-01

Full Text Available Victoria Mary Lendrum CohenSt. Bartholomew’s and Moorfields Eye Hospital, London UKAbstract: Most lymphomas that involve the ocular adnexal structure are low grade, B cell, non-Hodgkin’s lymphomas. The treatment depends upon the grade and stage of the disease. High grade lymhoma requires treatment with systemic chemotherapy whereas the localized low grade (extranodal marginal zone lymphoma can be successfully managed with local radiotherapy. Chlamydia psittaci infection is associated with low grade ocular lymphoma; however there is wide geographic variation in the strength of this association. Blanket antibiotic therapy is not advised unless there is proof of an infective agent. The monoclonal antibody, rituximab, may be successful for CD20 positive lymphoma, although it is likely that rituximab will have better long-term results when used in combination with systemic chemotherapy.Keywords: ocular adnexal lymphoma, mucosa associated lymphoid tissue, extranodal marginal zone lymphoma, Chlamydia psittaci, rituximab, radiotherapy, chemotherapy

Effect of Rituximab in Patients With Leucine-Rich, Glioma-Inactivated 1 Antibody–Associated Encephalopathy

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Irani, Sarosh R.; Gelfand, Jeffrey M.; Bettcher, Brianne M.; Singhal, Neel S.; Geschwind, Michael D.

2015-01-01

IMPORTANCE This observational study describes the efficacy and safety of rituximab in 5 patients with voltage-gated potassium channel (VGKC)–complex/leucine-rich, glioma-inactivated 1 (LGI1) antibody–associated encephalopathy. Rituximab is a monoclonal antibody that targets CD20 and is used to treat other neurologic and nonneurologic diseases. OBSERVATIONS This case series reports sequential seizure frequencies, modified Rankin Scale scores, and VGKC-complex antibody titers in 5 adult patients (median age, 65 years; range, 48–73 years) treated with rituximab. Median time from symptom onset to rituximab initiation was 414 days (range, 312–851 days). One patient showed a rapid clinical improvement after treatment with rituximab alone and experienced a rituximab-responsive clinical relapse. Another showed possible improvement on neuropsychometric memory indexes after rituximab therapy. In contrast, all patients showed robust responses to treatment with glucocorticoids, intravenous immunoglobulins, and/or plasma exchange at some point in their illness. Treatment with glucocorticoids—less so with intravenous immunoglobulins and plasma exchange—was associated with the most marked reductions in VGKC-complex antibodies. The only patient who did not receive glucocorticoids showed the poorest clinical and serologic responses. CONCLUSIONS AND RELEVANCE Rituximab was well tolerated in this predominantly older adult patient population and may be an effective option for some patients with LGI1 antibody–associated encephalopathy. Glucocorticoid therapy appears particularly efficacious. Earlier rituximab administration and randomized trials are required to formally assess efficacy. PMID:24842754

Neuropsychological evaluation of patients with inoperable non-small cell lung cancer treated with combination chemotherapy or radiotherapy

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Kaasa, S; Olsnes, B T; Mastekaasa, A

1988-01-01

Neuropsychological tests were used to evaluate possible central nervous system dysfunction in patients treated with chemotherapy. Ninety-five patients with non-small cell lung cancer limited disease were randomized to either radiotherapy (2.8 Gyx15) or combination chemotherapy with cisplatin and etoposide. In order to evaluate cognitive functions three neuropsychological tests were applied: Trail Making, Benton Visual Retention Test and Verbal Learning. Changes in the patients' test scores before and after treatment were compared. The chemotherapy patients showed reduced performance on some of the neuropsychological tests compared to the radiotherapy group. This indicates a treatment related effect on the central nervous system, possibly caused by the combination chemotherapy.

Neuropsychological evaluation of patients with inoperable non-small cell lung cancer treated with combination chemotherapy or radiotherapy

International Nuclear Information System (INIS)

Kaasa, S.; Olsnes, B.T.; Mastekaasa, A.

1988-01-01

Neuropsychological tests were used to evaluate possible central nervous system dysfunction in patients treated with chemotherapy. Ninety-five patients with non-small cell lung cancer limited disease were randomized to either radiotherapy (2.8 Gyx15) or combination chemotherapy with cisplatin and etoposide. In order to evaluate cognitive functions three neuropsychological tests were applied: Trail Making, Benton Visual Retention Test and Verbal Learning. Changes in the patients' test scores before and after treatment were compared. The chemotherapy patients showed reduced performance on some of the neuropsychological tests compared to the radiotherapy group. This indicates a treatment related effect on the central nervous system, possibly caused by the combination chemotherapy. (orig.)

Combination chemotherapy with Regorafenib in metastatic colorectal cancer treatment: A single center, retrospective study.

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Chun-Yu Lin

Full Text Available Regorafenib has been demonstrated as effective in refractory metastatic colorectal cancer. Combination use with chemotherapy has not been reported. We examined the efficacy and safety of adding chemotherapy to Regorafenib for the treatment of metastatic colorectal cancer(mCRC patients.We recruited mCRC patients at our institute who received either regorafenib monotherapy or regorafenib in combination with other chemotherapies. All patients had received chemo and target therapies and presented with disease progression before regorafenib treatment. The primary end point was overall survival.Between September1, 2015 and May 31, 2017, 100 mCRC patients at our institute received regorafenib treatment. 39 patients were excluded due to poor performance, lack of timely treatment, or inadequate clinical data. A total of 34 patients received regorafenib combined with other chemotherapies, and 27 patients received regorafenib alone. Median follow up time was 10.4 and 6.1 months, respectively. The primary end point of median OS was higher in the combination group than in the single use group (20.9m vs 10.3m, p = 0.015. The most frequent adverse events were hand-foot skin reactions(16[47.1%]vs 12[44.4%], fatigue(6[17.6%] vs 7[25.9%], gastrointestinal discomfort (7[20.6%] vs 6[22.2%], neutropenia (4[11.8%] vs 1[3.7%], diarrhea(4[11.8%] vs 1[3.7%], and mucositis(5[14.7%] vs 1[3.7%].The present study showed the efficacy and side effects of regorafenib combination treatment. Superiority in median OS and median PFS was noted in the combination group. The sampling difference between the study and observation groups effects justifies the comparison. Further clinical evidence of combination therapy efficacy is pending future studies.

Combination chemotherapy with Regorafenib in metastatic colorectal cancer treatment: A single center, retrospective study.

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Lin, Chun-Yu; Lin, Tseng-Hsi; Chen, Chou-Chen; Chen, Ming-Cheng; Chen, Chou-Pin

2018-01-01

Regorafenib has been demonstrated as effective in refractory metastatic colorectal cancer. Combination use with chemotherapy has not been reported. We examined the efficacy and safety of adding chemotherapy to Regorafenib for the treatment of metastatic colorectal cancer(mCRC) patients. We recruited mCRC patients at our institute who received either regorafenib monotherapy or regorafenib in combination with other chemotherapies. All patients had received chemo and target therapies and presented with disease progression before regorafenib treatment. The primary end point was overall survival. Between September1, 2015 and May 31, 2017, 100 mCRC patients at our institute received regorafenib treatment. 39 patients were excluded due to poor performance, lack of timely treatment, or inadequate clinical data. A total of 34 patients received regorafenib combined with other chemotherapies, and 27 patients received regorafenib alone. Median follow up time was 10.4 and 6.1 months, respectively. The primary end point of median OS was higher in the combination group than in the single use group (20.9m vs 10.3m, p = 0.015). The most frequent adverse events were hand-foot skin reactions(16[47.1%]vs 12[44.4%]), fatigue(6[17.6%] vs 7[25.9%]), gastrointestinal discomfort (7[20.6%] vs 6[22.2%]), neutropenia (4[11.8%] vs 1[3.7%]), diarrhea(4[11.8%] vs 1[3.7%]), and mucositis(5[14.7%] vs 1[3.7%]). The present study showed the efficacy and side effects of regorafenib combination treatment. Superiority in median OS and median PFS was noted in the combination group. The sampling difference between the study and observation groups effects justifies the comparison. Further clinical evidence of combination therapy efficacy is pending future studies.

Combination chemotherapy with Regorafenib in metastatic colorectal cancer treatment: A single center, retrospective study

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Lin, Chun-Yu; Lin, Tseng-Hsi; Chen, Chou-Chen; Chen, Ming-Cheng

2018-01-01

Background Regorafenib has been demonstrated as effective in refractory metastatic colorectal cancer. Combination use with chemotherapy has not been reported. We examined the efficacy and safety of adding chemotherapy to Regorafenib for the treatment of metastatic colorectal cancer(mCRC) patients. Methods We recruited mCRC patients at our institute who received either regorafenib monotherapy or regorafenib in combination with other chemotherapies. All patients had received chemo and target therapies and presented with disease progression before regorafenib treatment. The primary end point was overall survival. Findings Between September1, 2015 and May 31, 2017, 100 mCRC patients at our institute received regorafenib treatment. 39 patients were excluded due to poor performance, lack of timely treatment, or inadequate clinical data. A total of 34 patients received regorafenib combined with other chemotherapies, and 27 patients received regorafenib alone. Median follow up time was 10.4 and 6.1 months, respectively. The primary end point of median OS was higher in the combination group than in the single use group (20.9m vs 10.3m, p = 0.015). The most frequent adverse events were hand-foot skin reactions(16[47.1%]vs 12[44.4%]), fatigue(6[17.6%] vs 7[25.9%]), gastrointestinal discomfort (7[20.6%] vs 6[22.2%]), neutropenia (4[11.8%] vs 1[3.7%]), diarrhea(4[11.8%] vs 1[3.7%]), and mucositis(5[14.7%] vs 1[3.7%]). Conclusion The present study showed the efficacy and side effects of regorafenib combination treatment. Superiority in median OS and median PFS was noted in the combination group. The sampling difference between the study and observation groups effects justifies the comparison. Further clinical evidence of combination therapy efficacy is pending future studies. PMID:29304109

A combined radiation and platinum chemotherapy for esophageal carcinoma

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Takamura, Akio; Saito, Hiroya; Sakurai, Yasuo; Horio, Keiji; Mizoe, Junetsu.

1993-01-01

The prognosis of the patients with advanced esophageal carcinoma treated by definitive radiotherapy is still dismal with a reported 5-year survival rate of 5-10% in most series. Since 1986, combined radiotherapy with chemotherapy using platinum analogue was initiated at Asahikawa and Obihiro Kosei Hospitals in order to improve local-regional control and the survival of the patients. From 1980 to 1992, 81 patients with unresectable esophageal carcinoma were treated with radiotherapy. Since April 1986, 37 out of the 81 patients received both radiotherapy and chemotherapy with platinum. Platinum was used during the course of radiotherapy. The method of administration of platinum was as follows; Cisplatin intravenously (50 mg, weekly, total 200 mg) in 9 patients, Carboplatin intravenously (100-150 mg, weekly, total 400-900 mg) in 11 patients and Cisplatin intraarterially (100 mg, at a 3-4 week interval, total 100-300 mg) in 17 patients. These 37 patients (Group A) were compared to 44 patients treated by radiotherapy alone (Group B) with respect to initial response and survival rate. Response was defined according to the guidelines recommended by Japanese Society for Esophageal Diseases. Response rates were 59.1% (19 CR and 7 PR) in Group B and 70.3% (7 CR and 19 PR) in Group A. Primary relapse-free rates were 36.4% in Group B and 37.8% in Group A. The cumulative survival at 3 years were 11.7% in Group B and 10.6% in Group A. Enhancement of side effects by chemotherapy was minimal and acceptable. Improvement of local-regional control and survival was not obvious by adding a concomitant platinum-chemotherapy. A definite conclusion, however, could not be drawn because of the retrospective, non-controlled nature of this study. Introduction of more intensive, multiple agents chemotherapy seems necessary if one aims at improving the results. (author)

Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis.

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Miserocchi, Elisabetta; Modorati, Giulio; Berchicci, Luigi; Pontikaki, Irene; Meroni, Pierluigi; Gerloni, Valeria

2016-06-01

To evaluate retrospectively the long-term efficacy of rituximab in patients with severe juvenile idiopathic arthritis (JIA)-associated uveitis. Eight patients (15 eyes) with severe and longstanding JIA uveitis, who had an inadequate response in controlling uveitis to one or more biologic agents including tumour necrosis factor blockers and abatacept, received rituximab therapy. Rituximab was given at a dose of 1000 mg per infusion on days 1 and 15 and then every 6 months. Clinical responses to treatment, including decrease in uveitis activity, visual acuity changes, reduction of concomitant local and systemic corticosteroid and/or immunosuppressants, and occurrence of adverse events, were assessed. Eight patients with a mean±SD age of 22.8±5.5 years were treated. The mean ocular disease duration was 17.7 years; the mean±SD follow-up time on rituximab was 44.75±4.9 months; and the mean number of rituximab infusions received was 8.75 (range 6-12). All patients achieved complete control of uveitis, but in two patients rituximab was discontinued due to inefficacy in treating arthritis. The decrease in uveitis activity was evident 4-5 months after the first infusion. Systemic corticosteroids and immunosuppressants used in association with rituximab were discontinued in five patients at the end of follow-up. None of the patients experienced visual worsening during the follow-up. No drug-related complications were encountered. Rituximab may be a promising effective treatment option for refractory uveitis associated with JIA leading to long-term quiescence of uveitis, particularly for patients who have not previously responded to other biologic therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Application of Translational Medicine Theory in Chinese Materia Medica: Effect and Mechanism of Mahuang and Wuweizi on Pulmonary Fibrosis

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Hai-zhi QIN

2015-06-01

Full Text Available Objective: To explore the clinical efficacy and safety of rituximab combined with chemotherapy and single chemotherapy for diffuse large B cell lymphoma (DLBCL. Methods: A total of 97 patients with DLBCL were selected. Patients treated by single chemotherapy were designed as control group, while those by rituximab combined with chemotherapy as observational group. All patients were treated for at least 4 cycles. The short-term and long-term efficacy and related adverse reactions of 2 groups were observed. Results: The rate of complete remission (CR in observational group was significantly higher than in control group (χ2=4.6589, P=0.0309. However, there was no significant difference in objective remission rate (ORR between 2 groups (P=0.3651. The rates of 3-year overall survival (OS, progression-free survival (PFS and disease-free survival (DFS were 80.30% (53/66, 69.70% (46/66 and 59.09% (39/66 in observational group, and 61.29% (19/31, 58.06% (18/31 and 58.06% (18/31 in control group, respectively. The OS in observational group was significantly longer than in control group (P=0.035. However, there was no significant difference in PFS, DFS and rate adverse reactions between 2 groups (P=0.089; P=0.438; χ2=0.1562, P=0.6927. Conclusion: Rituximab combined with chemotherapy can improve the efficacy of DLBCL without increasing the adverse reactions, which can be used as the first-line treatment for DLBCL, thus deserving to be widely applied in clinic.

Intra-arterial and intra-venous chemotherapy combined with radiation in the treatment of brain tumours

International Nuclear Information System (INIS)

Watne, K.

1992-01-01

The present investigations were undertaken to study the effect of combining different modalities of chemotherapy with radiation in post-operative treatment of brain tumours. The conclusions and clinical implication of the investigations are as follows: The combination of combined intra-arterial chemotherapy followed by radiation leads to an increased median survival with more long term survivors in patients with anaplastic astrocytomas and in patients older than 40 years with astrocytomas. In patients with glioblastoma multiforme, this modality of treatment do not improve median survival, but an increased number of long-term survivors may be seen. Patients younger than 40 years with astrocytomas do not benefit from this modality of treatment. A parallelism exists between sensitivity to chemotherapy and response to radiotherapy. Patients who will benefit from the treatment may be selected early, normally two months after treatment start. Combining intra-arterial chemotherapy and radiation does not lead to an increased incidence of adverse CNS reactions. Specific transient abnormalities in the brain may occur during the first year after treatment and may be misinterpreted as tumour recurrence. EEG may be valuable in predicting adverse CNS reactions following treatment. Nuclear brain scan may be of valuable in selecting the patients who are in danger of developing adverse CNS reactions. Intra-arterial chemotherapy does have an effect in patients with brain tumours who have recurrent tumour after radiation. The most important prognostic factors are age, corticosteroid dependency at treatment start, performance status, histology and frontal lobe location. 103 refs., 2 tabs

Cyclophosphamide-refractory scleroderma-associated interstitial lung disease: remarkable clinical and radiological response to a single course of rituximab combined with high-dose corticosteroids.

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Haroon, Muhammad

2011-10-01

We would like to report our experience of using rituximab in cyclophosphamide refractory, rapidly progressive interstitial lung disease (ILD) in a patient with limited scleroderma. A 40-year-old man presented with 10-week history of inflammatory polyarthritis, which responded to a short course of oral corticosteroids. However, 3 weeks later, he developed new onset of exertional dyspnoea. High-resolution CT of the thorax was suggestive of early ILD. Surgical lung biopsy showed features of fibrotic non-specific interstitial pneumonia. He was diagnosed with scleroderma on the basis of: presence of anticentromere antibodies, Raynaud\\'s phenomenon, pulmonary fibrosis, digital oedema and hypomotility along with a dilated oesophagus. He was treated aggressively with pulse doses of corticosteroids and cyclophosphamide; however, his ILD continued to deteriorate. At this stage, he received rituximab (two pulses of 1 g each), which led to a gradual clinical improvement. Now, 12 months since his rituximab infusion, he walks 2 miles daily without any exertional dyspnoea.

Efficacy and safety of rituximab in neuromyelitis optica: Review of evidence

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Masoud Etemadifar

2017-01-01

Full Text Available Neuromyelitis optica (NMO is an autoimmune inflammatory disease of the central nervous system with preferential involvement in the optic nerve and spinal cord with a widespread spectrum of clinical features; multiple therapeutic agents have been used with different results. Recent evidence points to B-cell-mediated humoral immunity in the pathogenesis of NMO. Rituximab targets the CD20 antigen on B-cells. Treatment leads to profound B-cell depletion, principally over an antibody-dependent cell cytotoxicity mechanism. The aim of our study was to review clinical trials to elucidate the impact of rituximab on the relapse rate, Expanded Disability Status Scale (EDSS, and progression of disability in NMO. We performed a comprehensive review of all studies that evaluated clinical and paraclinical effects of rituximab on NMO. MEDLINE-PubMed, Web of Sciences, EMBASE, and Cochrane databases up to June 2016 included in our searches. In addition, reference lists from articles identified by search as well as a key review article to identify additional articles included in the study. Rituximab targets the CD20 antigen on B-cells and decreases attack frequency and severity in patients with NMO; however, it does not remove attacks, even when modifying treatment to achieve B-cell depletion. Most of the investigations revealed that EDSS significantly in all patients with rituximab treatment will be decreased after treatment with rituximab. No new or enlarged lesions or pathological gadolinium enhancement was observed in serial brain and spinal cord magnetic resonance imaging, except for those observed concomitantly with clinical relapses and the median length of spinal cord lesions was significantly reduced after therapy. Rituximab targets the CD20 antigen and decreases attack frequency and severity in patients with NMO.

A clinical study on combined modality therapy, radio-hyperthermo-chemotherapy, for pancreatic cancer

International Nuclear Information System (INIS)

Yamamoto, Yoshikazu

1989-01-01

A new multimodality therapy, radio-hyperthermo-chemotherapy, has been performed in a total of 31 pancreatic cancer patients with the purpose of improving treatment outcome. Combination of hyperthermia and chemotherapy was given as a pre-irradiation therapy in 7 resectable cancer patients. Among 24 unresectable cancer patients, 17 had irradiation in combination with hyperthermia and chemotherpay. Although both degeneration and necrosis of cancer cells were observed in all resectable cases at biopsy, these were not predictive of a better outcome. Of evaluable 17 patients with unresectable cancer, tumor regression was observed in 5 (29.4%). Although 22 patients had pain before therapy, 8 and 5 patients had remarkable and moderate pain relief, respectively, with therapy. Performance status was improved in 7 patients (29.2%). Survival rate at 12 months was still low (8.3%). However, the radio-hyperthermo-chemotherapy appears to help in increasing the quality of life in view of pain relief. (N.K.)

Rituximab as a first-line agent for the treatment of dermatomyositis.

LENUS (Irish Health Repository)

2012-02-01

B cells may play a pivotal role in the pathophysiology of DM, and reports have claimed that targeting B cells is a viable treatment option in patients with dermatomyositis. A 20-year-old girl presented in October 2007, with few weeks\\' history of proximal muscle weakness. Gottron\\'s papules were noted on her knuckles. She had normal inflammatory markers and negative autoantibody screen. Her CPK was 7,000 U\\/L (normal range 0-170) with an LDH of 1,300 U\\/L (normal range 266-500). EMG and muscle biopsy was consistent with active myositis. She had normal pulmonary function tests. HRCT showed no interstitial lung disease. She was started with 60 mg glucocorticoids (1 mg\\/kg), with a good clinical response. However, any attempt to taper down the steroid dose led to recurrence of her symptoms. The options of available immunosuppressive therapies, including the experimental usage of rituximab, were discussed with her; averse to long-term systemic treatments, she opted to try a course of rituximab. She had rituximab 1,000 mg on days 0 and 14, and her glucocorticoids were tapered in next few weeks. Now, 24 months since her rituximab infusions, she remains in complete clinical and biochemical remission and is naive to other immunosuppressive agents apart from glucocorticoids and rituximab. Depleting peripheral B cells with rituximab (one course) in our patient has led not only to complete resolution of muscle and skin disease (induction) but also remains off all immunosuppressives including glucocorticoids.

Effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion

Directory of Open Access Journals (Sweden)

Yu-Lin Zhao

2017-07-01

Full Text Available Objective: To study the effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion. Methods: A total of 62 patients with esophageal cancer who were treated in the hospital between January 2015 and December 2016 were collected and divided into control group and observation group according to random number table, with 31 cases in each group. Control group of patients received paclitaxel + cisplatin neoadjuvant chemotherapy + surgery, and observation group of patients accepted cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy + surgery. The differences in proliferation and invasion gene expression in the tumor tissue were compared between two groups of patients before and after chemotherapy. Results: Before chemotherapy, differences in proliferation and invasion gene expression in tumor tissue were not statistically significant between two groups of patients. After chemotherapy, proproliferation genes FOXA1, ABCE1, USP39 and Nestin mRNA expression in tumor tissue of observation group were significantly lower than those of control group; anti-proliferation genes PETN, KLF4, TSLC1 and AnnexinA2 mRNA expression were significantly higher than those of control group; pro-invasion genes γ-synuclein, CXCR4 and Snail mRNA expression were significantly lower than those of control group; anti-invasion genes CIAPIN1, Fez and Lrig1 mRNA expression were significantly higher than that of control group. Conclusions: Cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy can effectively inhibit the malignant degree of esophageal cancer cells and inhibit its proliferation and invasion.

Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial.

Science.gov (United States)

Wang, Michael L; Lee, Hun; Chuang, Hubert; Wagner-Bartak, Nicolaus; Hagemeister, Frederick; Westin, Jason; Fayad, Luis; Samaniego, Felipe; Turturro, Francesco; Oki, Yasuhiro; Chen, Wendy; Badillo, Maria; Nomie, Krystle; DeLa Rosa, Maria; Zhao, Donglu; Lam, Laura; Addison, Alicia; Zhang, Hui; Young, Ken H; Li, Shaoying; Santos, David; Medeiros, L Jeffrey; Champlin, Richard; Romaguera, Jorge; Zhang, Leo

2016-01-01

patient each. Adverse events led to discontinuation of therapy in five (10%) patients (atrial fibrillation in three [6%] patients, liver infection in one [2%], and bleeding in one [2%]). Two patients died while on-study from cardiac arrest and septic shock; the latter was deemed possibly related to treatment. Ibrutinib combined with rituximab is active and well tolerated in patients with relapsed or refractory mantle cell lymphoma. Our results provide preliminary evidence for the activity of this combination in clinical practice. A phase 3 trial is warranted for more definitive data. Pharmacyclics LLC, an AbbVie Company. Copyright © 2016 Elsevier Ltd. All rights reserved.

Higher World Health Organization grades of follicular lymphoma correlate with better outcome in two Nordic Lymphoma Group trials of rituximab without chemotherapy

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Wahlin, Björn Engelbrekt; Sundström, Christer; Sander, Birgitta

2014-01-01

Abstract A common treatment for follicular lymphoma is rituximab monotherapy. To identify patients for whom this regimen is adequate as first-line therapy, we applied the World Health Organization (WHO) classification for grading follicular lymphoma in a prospective central pathology review...... increased with the malignant cell size (p useful tool for personalized therapy....

Rituximab and Dexamethasone vs Dexamethasone Monotherapy in Newly Diagnosed Patients with Primary Immune Thrombocytopenia

DEFF Research Database (Denmark)

Gudbrandsdottir, Sif; Birgens, Henrik Sverre; Frederiksen, Henrik

2013-01-01

In this study, we report the results from the largest cohort to date of newly diagnosed adult immune thrombocytopenia patients randomized to treatment with dexamethasone alone or in combination with rituximab. Eligible were patients with platelet counts ≤25×10(9)/L or ≤50×10(9)/L with bleeding sy...

Treating Multiply Relapsed or Refractory Hairy Cell Leukemia

Science.gov (United States)

In this trial, patients with hairy cell leukemia who have not responded or relapsed after initial chemotherapy will be randomly assigned to receive rituximab combined with either pentostatin or bendamustine.

[Bendamustine-rituximab therapy is effective for transformed follicular lymphoma with significant expression of p53].

Science.gov (United States)

Kuroda, Hiroyuki; Jomen, Wataru; Miura, Shogo; Arihara, Yohei; Yamada, Michiko; Hirako, Tasuku; Abe, Tomoyuki; Sakurai, Tamaki; Fujii, Shigeyuki; Maeda, Masahiro; Fujita, Miri; Nagashima, Kazuo; Okagawa, Yutaka; Hoki, Toshifumi; Kato, Junji

2013-08-01

We describe a patient with transformed follicular lymphoma(FL), expressing p53 but remaining in complete remission(CR) due to bendamustine-rituximab(BR)therapy. She was a 64-year-old female diagnosed with stage IV FL(grade 3A)in July 2007 when she was admitted with right lower abdominal pain and body weight loss. Colonoscopy revealed Bauhin' valve lymphoma of the terminal ileum, and computed tomography(CT)scan showed lymphadenopathy, involving the cervical, mediastinal para-aortic lymph nodes and right tonsil. She received chemotherapy with eight courses of CHOP therapy with rituximab and achieved CR. Two and a half years later, mediastinal lymph node swelling relapsed, and ibritumomab tiuxetan therapy induced the second CR. After ten months, however, a third relapse occurred as a submucosal tumor(SMT)of the stomach. Gastric SMT biopsy showed diffuse large B cell lymphoma(DLBCL)transformation with immunohistochemical expression of p53. Although gastric SMT disappeared after radiotherapy, which achieved the third CR, lymph node swelling was detected again in the para-aortic and-iliac artery lymph nodes in September 2011. Subsequently, she was treated with five courses of BR therapy, because bendamustine had been reported to be effective for p53 gene-deficient B cell neoplasms. The therapy was successful and achieved the fourth CR, demonstrating that BR therapy was effective for p53-expressing DLBCL.

Long term survival with the combination of interferon and chemotherapy in metastatic melanoma

International Nuclear Information System (INIS)

Karagoz, B.; Bilgi, O.; Ozgun, A.; Emirzeoglu, L.; Celika, S.; Ozet, A.

2015-01-01

The prognosis of metastatic melanoma is poor. Pre-targeted treatment era, the combination of interferon-α (IF-α) plus chemotherapy had been used and have generally short response duration. Herein, we present a metastatic melanoma case that achieved long-term durable complete response (CR) IF-α plus chemotherapy and IF-α maintenance therapy and had lower Regulatory T (Treg) cells. A fifty-year old woman was admitted to the hospital with metastatic melanoma. Lactate dehydrogenase (LDH) level was 660 U/L. The percentage of CD4+CD25+ Treg cells was 2.4% in CD4+ lymphocytes. The IF-α plus chemotherapy and IF-α maintenance were administered. After six courses of chemotherapy, CR was achieved. Vitiligo and hypothyroidism occurred. The patient has remained in CR for approximately 7 years until second pleural metastases were detected and death. The patient has positive prognostic factors such as induction of auto immunity, small tumor volume, mild elevated LDH level, and lower Treg cell percentage. She survived long term with CR after IF-α treatment with concurrent chemotherapy and maintenance. IF-α plus chemotherapy may be a treatment option for metastatic melanoma in selected cases who cannot reach new targeted drugs

Rituximab para la oftalmopatía asociada a la tiroides

Directory of Open Access Journals (Sweden)

Neda Minakaran

2013-09-01

Conclusiones de los autores: Actualmente no hay pruebas suficientes para apoyar la administración de rituximab en los pacientes con OAT. Se necesitan ECA grandes que investiguen rituximab versus placebo o corticosteroides en pacientes con OAT activo para hacer valoraciones adecuadas sobre la eficacia y la seguridad de este tratamiento nuevo para esta enfermedad.

Outcome of combination chemotherapy in extensive stage small-cell lung cancer

DEFF Research Database (Denmark)

Lassen, U N; Hirsch, F R; Osterlind, K

1998-01-01

During the past two decades many different treatment regimens of combination chemotherapy have been applied in extensive stage small-cell lung cancer (SCLC). This study was carried out to identify whether these modifications have resulted in an improved overall survival for extensive stage during...

Successful treatment of ovarian cancer with apatinib combined with chemotherapy: A case report.

Science.gov (United States)

Zhang, Mingzi; Tian, Zhongkai; Sun, Yehong

2017-11-01

The standard treatment for ovarian cancer is chemotherapy with 2 drugs (taxanes and platinum drugs). However, the traditional combination of the 2 drugs has many adverse effects (AEs) and the cancer cells will quickly become resistant to the drugs. Apatinib is a small-molecule antiangiogenic agent which has shown promising therapeutic effects against diverse tumor types, but it still remains unknown whether apatinib has an antitumor effect in patients with ovarian cancer. Herein, we present a successfully treated case of ovarian cancer using chemotherapy and apatinib, in order to demonstrate the effectiveness of this new combined regimen in ovarian cancer. A 51-year-old Chinese woman presented with ovarian cancer >4.5 years. The disease and the cancer antigen 125 (CA-125) had been controlled well by surgical treatment and following chemotherapy. However, the drugs could not control the disease anymore as the CA-125 level was significantly increasing. Ovarian cancer. The patient was treated with apatinib combined with epirubicin. Apatinib was administered orally, at an initial daily dose of 500 mg, and was then reduced to 250 mg qd after the appearance of intolerable hand-foot syndrome (HFS) and oral ulcer. Then, the oral ulcer disappeared and the HFS was controlled by dose adjustment, oral vitamin B6, and hand cream application. The CA-125 reverted to the normal value after treatment with the new regimen. Magnetic resonance imaging showed that the original tumor lesions had disappeared. Apatinib monotherapy as maintenance therapy was then used to successfully control the cancer with a complete response. Our study is the first, to our knowledge, to report the therapeutic effects of apatinib and epirubicin on ovarian cancer. Apatinib combined with chemotherapy and apatinib monotherapy as maintenance therapy could be a new therapeutic strategy for ovarian cancer, especially adenocarcinomas.

Adverse drug reactions after intravenous rituximab infusion are more common in hematologic malignancies than in autoimmune disorders and can be predicted by the combination of few clinical and laboratory parameters: results from a retrospective, multicenter study of 374 patients.

Science.gov (United States)

D'Arena, Giovanni; Simeon, Vittorio; Laurenti, Luca; Cimminiello, Michele; Innocenti, Idanna; Gilio, Michele; Padula, Angela; Vigliotti, Maria Luigia; De Lorenzo, Sonya; Loseto, Giacomo; Passarelli, Anna; Di Minno, Matteo Nicola Dario; Tucci, Marco; De Feo, Vincenzo; D'Auria, Fiorella; Silvestris, Francesco; Di Minno, Giovanni; Musto, Pellegrino

2017-11-01

Rituximab is an effective treatment for CD20 + B-cell malignancies and autoimmune disorders. However, adverse drug reactions (ADRs) may occur after rituximab infusion, causing, in rare cases, its discontinuation. In this multicenter, retrospective study, among 374 patients treated with rituximab i.v., 23.5% experienced ADRs. Mean follow-up was 20.6 months (range 8-135). Overall, ADRs were significantly more frequent in non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemias (25-35.9%), than in autoimmune diseases (9.4-17.5%) (p < .0001). Grade 3-4 toxicity was observed in eight patients (2.1%), and in four of them (1% of all patients) definitive drug discontinuation was necessary. Interestingly, three groups of patients with different risk of developing ADR were identified, according to a predictive heat-map developed combining four parameters (splenomegaly, history of allergy, hemoglobin levels and gender) selected by multivariate analysis. This model may be useful in identifying patients at higher risk of ADRs, needing appropriate preventing therapies.

Is there any advantage to combined trastuzumab and chemotherapy in perioperative setting her 2neu positive localized gastric adenocarcinoma?

Directory of Open Access Journals (Sweden)

Albouzidi Abderrahmane

2011-09-01

Full Text Available Abstract We report here a 44-year-old Moroccan man with resectable gastric adenocarcinoma with overexpression of human epidermal growth factor receptor 2 (HER2 by immunohistochemistry who was treated with trastuzumab in combination with chemotherapy in perioperative setting. He received 3 cycles of neoadjuvant chemotherapy consisting of trastuzumab, oxaliplatin, and capecitabine. Afterwards, he received total gastrectomy with extended D2 lymphadenectomy without spleno-pancreatectomy. A pathologic complete response was obtained with a combination of trastuzumab and oxaliplatin and capecitabine. He received 3 more cycles of trastuzumab containing regimen postoperatively. We conclude that resectable gastric carcinoma with overexpression of the c-erbB-2 protein should ideally be managed with perioperative combination of trastuzumab with chemotherapy. Further research to evaluate trastuzumab in combination with chemotherapy regimens in the perioperative and adjuvant setting is urgently needed.

Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)).

Science.gov (United States)

Emery, P; Deodhar, A; Rigby, W F; Isaacs, J D; Combe, B; Racewicz, A J; Latinis, K; Abud-Mendoza, C; Szczepanski, L J; Roschmann, R A; Chen, A; Armstrong, G K; Douglass, W; Tyrrell, H

2010-09-01

This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. Patients with active disease on stable MTX (10-25 mg/week) were randomised to rituximab 2 x 500 mg (n=168), rituximab 2 x 1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) > or =2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2 x 500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2 x 500 mg) + MTX, rituximab (2 x 1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. Rituximab (at 2 x 500 mg and 2 x 1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses.

Clinical comparative investigation using intensity-modulated radiotherapy combined with concurrent chemotherapy for the local advanced nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Zhao Yingchao; Dai Xiaofang; Wu Gang; Zhao Yanxia; Luo Ming

2009-01-01

Objective: To research the early effects and side-effects of the local advanced nasopharyngeal carcinoma patients using intensity-modulated radiotherapy (IMRT) combined with concurrent chemotherapy. Methods: From January 2005 to January 2007, 60 patients with nasopharyngeal carcinoma of stage m-IV b were received IMRT combined with concurrent chemotherapy in our center. Sixty patients were divided into paclitaxel concurrent group (32 patients) and cisplatin concurrent group (28 patients). The prescribing doses of the primary tumor were 68-72 Gy for each group. The patients of paclitaxel concurrent group received 5-7 times pacitaxel liposome chemotherapy of 30 mg · m -2 ·. The patients of cisplatin concurrent group received 5-7 times cisplatin chemotherapy of 30 mg · m -2 · week -1 . Results: As to the side-effects, the patients of the cisplatin concurrent group got earlier radiodermatitis and radiation-induced mucositis but also got significantly higher rate of radiodermatitis, radiation-induced mucositis, radiation-induced leucopenia and gastrointestinal toxicity, as well as the loss of weight. No significant difference was found on liver and renal functions between two groups.Four patients (12.5%) of the paclitaxel concurrent group were broken-off, which was much better than the cisplatin concurrent group. There was no significant difference on the specific length of break-off time, the 2-year overall survival rate and the 2-year diseaee-free survival rate between two groups. Conclusions: IMRT combined with concurrent chemotherapy of paclitaxel liposome for local advanced nasopharyngeal carcinoma results in less side-effects and better tolerance than IMRT combined with concurrent cisplatin chemotherapy. (authors)

Malignant gliomas treated after surgery by combination chemotherapy and delayed radiation therapy. Pt. 2

International Nuclear Information System (INIS)

Poisson, M.; Mashaly, R.; Pertuiset, B.F.; Metzger, J.

1979-01-01

34 patients operated on for malignant gliomas were successively treated by combination chemotherapy with VM 26 and CCNU and conventional radiation therapy with an average dosage of 5,800 rads, six months after surgery. The general and haematological tolerance of delayed irradiation after chemotherapy was satisfactory. Twelve patients developed neurological complications during or after irradiation. The complications were early in 10 cases, and delayed in 2. They were probably due to tumour growth in five cases, and secondary to irradiation in seven. In four of the seven cases the preradiation chemotherapy seemed to potentiate the radiation effect on the central nervous system. (author)

Regional hyperthermia combined with chemotherapy in paediatric, adolescent and young adult patients: current and future perspectives

International Nuclear Information System (INIS)

Seifert, Georg; Budach, Volker; Keilholz, Ulrich; Wust, Peter; Eggert, Angelika; Ghadjar, Pirus

2016-01-01

Here we evaluate the current status of clinical research on regional hyperthermia (RHT) in combination with chemotherapy or radiation therapy in paediatric oncology. Data were identified in searches of MEDLINE, Current Contents, PubMed, and references from relevant articles using medical subject headings including hyperthermia, cancer, paediatric oncology, children, radiation therapy and chemotherapy. Currently, only two RHT centres exist in Europe which treat children. Clinical RHT research in paediatric oncology has as yet been limited to children with sarcomas and germ cell tumours that respond poorly to or recur after chemotherapy. RHT is a safe and effective treatment delivering local thermic effects, which may also stimulate immunological processes via heat-shock protein reactions. RHT is used chiefly in children and adolescents with sarcomas or germ cell tumours located in the abdomino-pelvic region, chest wall or extremities to improve operability or render the tumour operable. It could potentially be combined with radiation therapy in a post-operative R1 setting where more radical surgery is not possible or combined with chemotherapy instead of radiation therapy in cases where the necessary radiation dose is impossible to achieve or would have mutilating consequences. RHT might also be an option for chemotherapy intensification in the neoadjuvant first-line treatment setting for children and adolescents, as was recently reflected in the promising long-term outcome data in adults with high-risk soft tissue sarcomas (EORTC 62961/ESHO trial). The limited data available indicate that combining RHT with chemotherapy is a promising option to treat germ cell tumours and, potentially, sarcomas. RHT may also be beneficial in first-line therapy in children, adolescents and young adults. The research should focus on optimising necessary technical demands and then initiate several clinical trials incorporating RHT into interdisciplinary treatment of children

Combined regional chemotherapy and radiation therapy in the treatment of epidermoid carcinoma in the oro-facial region

Energy Technology Data Exchange (ETDEWEB)

Danko, J; Satko, I [Komenskeho Univ., Bratislava (Czechoslovakia). Lekarska Fakulta; Durkovsky, J [Institute of Clinical Oncology, Bratislava (Czechoslovakia)

1979-01-01

Treatment was studied of oro-facial epidermoid carcinoma by combined chemo- and radiotherapy and eventual surgery. Cytostatic drugs were applied intraarterially. After a monocytostatic treatment trial with Methotrexate (MTX), a combined cytostatic program was developed alternating two cytostatic drugs, viz., MTX and Bleomycin (BLM). The usefulness of chemotherapy and its inclusion in the treatment of epidermoid carcinoma in the oro-facial region was found justified for combined therapy. The selected intraarterial administration, however, is not suitable for routine application. For this reason, the combination irradiation or surgical therapy with chemotherapy was adopted.

Ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study

Science.gov (United States)

Burger, Jan A.; Keating, Michael J.; Wierda, William G.; Hartmann, Elena; Hoellenriegel, Julia; Rosin, Nathalie Y.; de Weerdt, Iris; Jeyakumar, Ghayathri; Ferrajoli, Alessandra; Cardenas-Turanzas, Marylou; Lerner, Susan; Jorgensen, Jeffrey L; Nogueras-González, Graciela M.; Zacharian, Gracy; Huang, Xuelin; Kantarjian, Hagop; Garg, Naveen; Rosenwald, Andreas; O’Brien, Susan

2014-01-01

Summary Background Ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), is an effective therapy for patients with relapsed chronic lymphocytic leukemia (CLL). We investigated the activity and safety of the combination of ibrutinib with the monoclonal antibody rituximab (iR) in patients with high-risk CLL. Methods In this single-arm, phase 2 studywe enrolled 40 patients with high-risk CLL at MD Anderson Cancer Center, Houston, Texas, USA. Patients with symptomatic CLL requiring therapy received 28 day cycles of once-daily ibrutinib 420 mg , together with rituximab (weekly during cycle 1, then once per cycle until cycle 6), followed by continuous single-agent ibrutinib. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01520519 and is no longer accruing patients. Findings Between February 28, 2012 and September 11, 2012, we enrolled 40 CLL patients with high-risk disease features. 20 patients had del17p or TP53 mutations (16 previously treated, 4 untreated), 13 had relapsed CLL with del11q, and 7 patients a PFS infections occurred in 4 patients (10%), no grade 4 or 5 infections occurred. At 18 months, the Kaplan Meier estimate of progression-free survival was 78% (95% CI 60.6–88.5) (del[17p] or TP53 mutation: 72%, 95% CI: 45.6–87.6) Interpretation Ibrutinib in combination with rituximab is a well-tolerated regimen for patients with high-risk CLL. It induces high rates of remissions and has positive impact on QOL in this difficult-to-treat patient population. These encouraging data merit further investigation of the added benefit of rituximab as combination partner for ibrutinib in an ongoing randomized trial, in which single-agent ibrutinib is compared to iR combination therapy (NCT02007044). Funding Pharmacyclics, Inc., Cancer Prevention and Research Institute of Texas (CPRIT), Leukemia & Lymphoma Society, NCI Grant P30 CA

Progression of structural damage is not related to rituximab serum levels in rheumatoid arthritis patients

NARCIS (Netherlands)

Boumans, Maria; Teng, Onno; Thurlings, Rogier; Bijlsma, Johannes; Gerlag, Danielle; Huizinga, Tom; Vos, Koen; Stapel, Steven; Wolbink, Gertjan; Tekstra, Janneke; van Laar, Jaap; Tak, Paul P.

2013-01-01

The most cost-effective dosing regimen for rituximab treatment in RA is currently unknown. The objective of this study is to determine whether low rituximab serum levels are associated with progression of structural damage in RA patients. Sixty-two RA patients were treated with rituximab in three

Sequential rituximab and omalizumab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

Science.gov (United States)

Aguirre-Valencia, David; Posso-Osorio, Iván; Bravo, Juan-Carlos; Bonilla-Abadía, Fabio; Tobón, Gabriel J; Cañas, Carlos A

2017-09-01

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome (CSS), is a small vessel vasculitis associated with eosinophilia and asthma. Clinical manifestations commonly seen in patients presenting with EGPA range from upper airway and lung involvement to neurological, cardiac, cutaneous, and renal manifestations. Treatment for severe presentations includes steroids, cyclophosphamide, plasmapheresis, and recently, rituximab. Rituximab is associated with a good response in the treatment of vasculitis, but a variable response for the control of allergic symptoms. Here, we report a 16-year-old female patient with severe EGPA (gastrointestinal and cutaneous vasculitis, rhinitis and asthma) refractory to conventional treatment. She was treated with rituximab, which enabled rapid control of the vasculitis component of the disease, but there was no response to rhinitis and asthma. Additionally, she developed severe bronchospasm during rituximab infusion. Sequential rituximab and omalizumab were initiated, leading to remission of all manifestations of vasculitis, rhinitis, and asthma, in addition to bronchospasm related to rituximab infusion.

Single-dose Rituximab Therapy for Refractory Idiopathic Membranous Nephropathy: A Single-center Experience

OpenAIRE

Katsuno, Takayuki; Ozaki, Takenori; Kim, Hangsoo; Kato, Noritoshi; Suzuki, Yasuhiro; Akiyama, Shinichi; Ishimoto, Takuji; Kosugi, Tomoki; Tsuboi, Naotake; Ito, Yasuhiko; Maruyama, Shoichi

2017-01-01

To date, a recognized treatment for refractory membranous nephropathy (MN) has not been established. Recently, several reports have indicated the efficacy of rituximab as a novel treatment option. However, only a few published accounts exist of rituximab therapy for idiopathic MN (IMN) in the Asian population. We present the cases of three IMN patients who were treated with single-dose rituximab after they showed no response to conventional therapies, including corticosteroids, cyclosporine, ...

Study On The Preparation Of 90Y-DTPA-Rituximab For Non-Hodgkin Lymphoma Treatment

International Nuclear Information System (INIS)

Nguyen Thi Thu; Duong Van Dong; Bui Van Cuong; Vo Thi Cam Hoa; Chu Van Khoa; Phan Quoc Thong

2011-01-01

Yttrium is one of the most useful radionuclides for radioimmunotherapeutic applications, especially labelling with monoclonal antibodies. Rituximab was bound to the DTPA chelating agent using Hnatowich methods. Cyclic anhydride DTPA (cDTPAa, 0.1 mg/ml) was dissolved in chloroform and was degassed under a stream of nitrogen for 30 minutes. Rituximab solution in 0.05 M bicarbonate buffer was immediately added and mixed for one minute at room temperature. The antibody Rituximab at different concentration (5 mg/ml and 10 mg/ml) was coupled with the cDTPAa, at molar ratios (cDTPAa : Rituximab) of 1:1, 3:1, 5:1, 10:1 and 20:1. The conjugation of DTPA-Rituximab mixture was labelled with Y-90, then using Sephadex G25 in order to determine coupling efficiency. Coupling efficiency at a 3:1 mole ratio was 70%. After purification, the conjugation DTPA-Rituximab was labeled with Y-90 in 0.5 M acetate buffer, pH 5, at room temperature. The labeling yield was about 99%. The radiochemical purity of 90 Y-DTPA-Rituximab was more than 98 % which determined by ITLC in 0.1 M acetate at pH 6 as mobile phase. The radiopharmaceuticals have been test for sterility, apyrogenicity and biodistribution. This is a potential radiopharmaceutical for clinical application in therapeutic Non Hodgkin Lymphoma treatments. (author)

Acute neurological worsening after Rituximab treatment in patients with anti-MAG neuropathy.

Science.gov (United States)

Sala, Emilie; Robert-Varvat, Florence; Paul, Stéphane; Camdessanché, Jean-Philippe; Antoine, Jean-Christophe

2014-10-15

Patients with peripheral neuropathy and anti-MAG monoclonal IgM may respond to Rituximab, a humanized monoclonal anti-CD20 antibody. We report on three patients with peripheral neuropathy and anti-MAG monoclonal IgM who deteriorated under Rituximab and reviewed seven previously published cases. Worsening was acute and severe, and occurred during the treatment period. All the patients improved after deterioration but at final evaluation only one was improved comparatively to baseline, five were worsened and four were stabilized. Deterioration was not clearly associated with an increase of the anti-MAG antibody titer. Two patients received Rituximab prior or after the course which induced worsening without adverse reaction. Although rare, acute worsening of the neuropathy can occur after Rituximab. The deterioration is however reversible within some weeks to several months. Copyright © 2014 Elsevier B.V. All rights reserved.

Combination therapy of gastric carcinoma with radiation and chemotherapy

Energy Technology Data Exchange (ETDEWEB)

Asakawa, Hiroshi; Otawa, Hirokazu; Yamada, Shogo; Matsumoto, Ko [Miyagi Prefectural Adult Disease Center, Natori (Japan)

1982-08-01

The concurrent combination therapy of radiation and chemotherapy was performed in a total of 134 cases of stomach cancer. Radiation response of tumor was remarkable in 35 (37%) of 95 cases, irradiated more than 5,000 rad. Yearly survival rates in 81 cases, in which the scheduled curative treatment was completed, were 63% in one, 31% in two, 21% in three, 17% in four and 13% in five years. These rates were intimately correlated to tumor size and cancer type. However, this combination therapy accompanied some fatal complications in a few percent. From the results, it was concluded that this combination therapy should be valuable to prolong the life of patients with gastric cancer, and that the curable indications for this treatment should be T1-T3: M0 cases with radio-responsive tumor.

Socioeconomic inequality in the use of rituximab therapy among non-Hodgkin lymphoma patients in Chinese public hospitals.

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Yu-Wen, Huang; Mei-Bian, Zhang; Xiang, Xu; Xiao-Hua, Xu; Quan, Zhou; Le, Jian

2014-03-01

Rituximab is a patient-paid effective monoclonal-antibody drug for non-Hodgkin lymphoma (NHL). Little is known in China, a country with unequal distribution of wealth and medical insurance systems, about the impact of socioeconomic status (SES) on selecting rituximab therapy in NHL patients. A total of 328 NHL inpatients in 2 public hospitals in Hangzhou were recruited and divided into 2 equal groups: with rituximab therapy and with no rituximab therapy group. Selection and frequency of rituximab therapy increased with duration of education and in urban citizens (P inequality in provision of rituximab therapy among Chinese NHL patients, and this was associated with differences in SES status. Effective measures are suggested to ameliorate the inequality issue.

[Rituximab: a new therapeutic alternative in Grave's disease].

Science.gov (United States)

Tello-Winniczuk, Nina; Díaz-Jouanen, Efraín

2011-01-01

Graves' disease is the most frequent cause of hyperthyroidism, affecting mainly young aged women, with an etiology of autoimmune basis. One of its manifestations, Graves' ophthalmopathy whose pathophysiology is unknown, represents one of the greatest therapeutic challenges in these patients, because they require aggressive treatment with steroids and multiple subsequent reconstructive surgeries in certain cases. It also represents a high burden to the health system. Drugs targeting B cells have been very effective for many autoimmune diseases. Rituximab is a murine humanized monoclonal antibody against CD20 + cells currently being studied in various autoimmune diseases including Graves' disease. The objective of this paper is to expose possible mechanisms by which rituximab could act in both hyperthyroidism and ophthalmopathy of Graves' disease, as well as the experience with its use acquired so far. The employment of rituximab in recently diagnosed patients or with mild ophthalmopathy is questionable with the evidence available today however, we think that it may have a role in refractory cases or those who have a contraindication for steroid use.

When Combined with Chemotherapy, Bevacizumab Is Associated with Increased Risk of Death

Science.gov (United States)

Cancer patients who receive the targeted therapy bevacizumab (Avastin) in combination with chemotherapy are at increased risk of serious side effects that may lead to death, according to a meta-analysis of 16 clinical trials that was published February 2,

Hyperthermia of locally advanced or recurrent gynecological cancer. The effect of combination with irradiation or chemotherapy

International Nuclear Information System (INIS)

Terashima, Hiromi; Imada, Hajime; Egashira, Kanji; Nakata, Hajime; Kunugita, Naoki; Matsuura, Yuusuke; Kashimura, Masamichi

1995-01-01

Between May 1986 and April 1994, 15 patients with advanced or recurrent gynecological cancer were treated with combined therapy of hyperthermia and irradiation or chemotherapy at UOEH Hospital. Initial cases were treated by hyperthermia combined with irradiation in 4 and with chemotherapy in 2. Recurrent 9 cases were treated by hyperthermia combined with chemotherapy or by hyperthermia alone. Radiotherapy was given in a conventional way 5 fractions per week and hyperthermia was performed using RF capacitive heating equipment, Thermotron RF-8, once or twice a week. Intratumoral temperature was measured by thermocouple inserted into the tumor and kept at 42-44degC for 30-40 minutes. Complete response (CR) and partial response (PR), defined as 50% or more regression, was obtained in 8/15 (53%). Response rates (CR+PR/all cases) were good in initially treated cases (5/6, 83%), irradiated cases (7/8, 88%) and cases hearted over 42degC (7/9, 78%). Combined therapy of hyperthermia and radiotherapy seemed to be useful for controlling advanced gynecological cancers. (author)

The search for therapeutic gain in the combination of radiotherapy and chemotherapy

International Nuclear Information System (INIS)

Steel, G.G.

1988-01-01

The literature on combined treatment with radiation and cytotoxic drugs in experimental tumours and normal tissues of laboratory animals is reviewed in the context of the four previously proposed mechanisms whereby a therapeutic advantage might be gained. There is evidence for strong time-dependent processes occurring in some normal tissues. In tumours, the evidence is much weaker and there is considerable disparity among experimental tumours in optimum timing. This review leads to the conclusion that the clinical use of drug-radiation combinations should not be based on an anticipated beneficial interaction; gain will most probably come from the best radiotherapy and the best chemotherapy given as far as possible independently. Deleterious interactions can be reduced by allowing a gap of some weeks between chemotherapy and radiotherapy and by avoiding drugs that are known to enhance radiation damage to the normal tissues that are irradiated. 131 refs.; 4 figs.; 5 tabs

Muscle myeloid type I interferon gene expression may predict therapeutic responses to rituximab in myositis patients.

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Nagaraju, Kanneboyina; Ghimbovschi, Svetlana; Rayavarapu, Sree; Phadke, Aditi; Rider, Lisa G; Hoffman, Eric P; Miller, Frederick W

2016-09-01

To identify muscle gene expression patterns that predict rituximab responses and assess the effects of rituximab on muscle gene expression in PM and DM. In an attempt to understand the molecular mechanism of response and non-response to rituximab therapy, we performed Affymetrix gene expression array analyses on muscle biopsy specimens taken before and after rituximab therapy from eight PM and two DM patients in the Rituximab in Myositis study. We also analysed selected muscle-infiltrating cell phenotypes in these biopsies by immunohistochemical staining. Partek and Ingenuity pathway analyses assessed the gene pathways and networks. Myeloid type I IFN signature genes were expressed at higher levels at baseline in the skeletal muscle of rituximab responders than in non-responders, whereas classic non-myeloid IFN signature genes were expressed at higher levels in non-responders at baseline. Also, rituximab responders have a greater reduction of the myeloid and non-myeloid type I IFN signatures than non-responders. The decrease in the type I IFN signature following administration of rituximab may be associated with the decreases in muscle-infiltrating CD19(+) B cells and CD68(+) macrophages in responders. Our findings suggest that high levels of myeloid type I IFN gene expression in skeletal muscle predict responses to rituximab in PM/DM and that rituximab responders also have a greater decrease in the expression of these genes. These data add further evidence to recent studies defining the type I IFN signature as both a predictor of therapeutic responses and a biomarker of myositis disease activity. Published by Oxford University Press on behalf British Society for Rheumatology 2016. This work is written by US Government employees and is in the public domain in the US.

[Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab].

Science.gov (United States)

Boin, C; Lambert, S; Thomann, P; Aujoulat, O; Kieffer, P

2016-06-01

Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Chemotherapy disruption of efficient radiotherapy

International Nuclear Information System (INIS)

Nervi, C.; Friedman, M.

1974-01-01

Studies on the use of chemotherapy in combination with radiotherapy are reviewed. Some topics discussed are: indications for the use of combined chemotherapy and radiotherapy; improvement of the therapeutic ratio following the use of methotrexate; advantages of preirradiation and postirradiation chemotherapy; side effects following simultaneous chemotherapy and radiotherapy; and effects of chemotherapy on cure rate of radiosensitive and radioresistant tumors. (U.S.)

Ibrutinib for patients with rituximab-refractory Waldenström's macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial.

Science.gov (United States)

Dimopoulos, Meletios A; Trotman, Judith; Tedeschi, Alessandra; Matous, Jeffrey V; Macdonald, David; Tam, Constantine; Tournilhac, Olivier; Ma, Shuo; Oriol, Albert; Heffner, Leonard T; Shustik, Chaim; García-Sanz, Ramón; Cornell, Robert F; de Larrea, Carlos Fernández; Castillo, Jorge J; Granell, Miquel; Kyrtsonis, Marie-Christine; Leblond, Veronique; Symeonidis, Argiris; Kastritis, Efstathios; Singh, Priyanka; Li, Jianling; Graef, Thorsten; Bilotti, Elizabeth; Treon, Steven; Buske, Christian

2017-02-01

öm Macroglobulinaemia, median number of previous therapies was four (IQR 2-6), and all were rituximab-refractory. At a median follow-up of 18·1 months (IQR 17·5-18·9), the proportion of patients with an overall response was 28 [90%] of 31 (22 [71%] of patients had a major response), the estimated 18 month progression-free survival rate was 86% (95% CI 66-94), and the estimated 18 month overall survival rate was 97% (95% CI 79-100). Baseline median haemoglobin of 10·3 g/dL (IQR 9·3-11·7) increased to 11·4 g/dL (10·9-12·4) after 4 weeks of ibrutinib treatment and reached 12·7 g/dL (11·8-13·4) at week 49. A clinically meaningful improvement from baseline in FACT-An score, anaemia subscale score, and the EQ-5D-5L were reported at all post-baseline visits. Time to next treatment will be presented at a later date. Common grade 3 or worse adverse events included neutropenia in four patients (13%), hypertension in three patients (10%), and anaemia, thrombocytopenia, and diarrhoea in two patients each (6%). Serious adverse events occurred in ten patients (32%) and were most often infections. Five (16%) patients discontinued ibrutinib: three due to progression and two due to adverse events, while the remaining 26 [84%] of patients are continuing ibrutinib at the time of this report. The sustained responses and median progression-free survival time, combined with a manageable toxicity profile observed with single-agent ibrutinib indicate that this chemotherapy-free approach is a potential new treatment choice for patients who had heavily pretreated, rituximab-refractory Waldenström's macroglobulinaemia. Pharmacyclics LLC, an AbbVie Company. Copyright © 2017 Elsevier Ltd. All rights reserved.

Female fertility following dose-adjusted EPOCH-R chemotherapy in primary mediastinal B-cell lymphomas.

Science.gov (United States)

Gharwan, Helen; Lai, Catherine; Grant, Cliona; Dunleavy, Kieron; Steinberg, Seth M; Shovlin, Margaret; Fojo, Tito; Wilson, Wyndham H

2016-07-01

We assessed fertility/gonadal function in premenopausal women treated with dose-adjusted EPOCH-Rituximab for untreated primary mediastinal B-cell lymphoma (PMBL). Eligible patents were ≤ 50 years and premenopausal. Serial reproductive histories were obtained and hormonal assays were performed on serum samples before, at the end of treatment and 4-18 months later. Twenty-eight eligible women had a median age (range) of 31 (21-50) years and were followed a median of 7.3 years. Of 23 patients who completed a questionnaire, 19 (83%) were and four were not menstruating prior to chemotherapy. Amenorrhea developed in 12 patients during chemotherapy. At > 1-year follow-up, 14/19 (74%) patients were menstruating, all years old, and six (43%) of these patients delivered healthy children. Hormonal assays showed ovarian dysfunction during chemotherapy in all patients with varying recovery at 4-18 months after treatment. Fertility was preserved in most women with ovarian failure confined to patients > 40 years old.

Combination therapy with hormonal, radiation and chemotherapy for stage C prostate cancer

International Nuclear Information System (INIS)

Iwasawa, Toshihisa; Matsumoto, Hidetsugu

1996-01-01

To improve the effectiveness of treatment for patients with stage C prostate cancer, therapy in combination with hormonal, radiation and chemotherapy was given for the initial period, and there after, hormonal therapy was continuously administered to 18 patients with chemotherapy and three patients without it. At the Social Health Insurance Medical Center, between May 1988 and August 1991, 21 patients were diagnosed to have stage C histologically confirmed adenocarcinoma of the prostate. The average age of the patients was 69.0 years. The tumor was well, moderate and poorly differentiated in 5, 6 and 10 patients, respectively. As hormonal therapy, orchiectomy was performed on 19 of the 21 patients. Furthermore, 11 patients were administered estramustine phosphate, 9 chlormadinone acetate, and one diethylstilbesterol diphosphate. As, radiation therapy, all patients were treated with AP-PA parallel opposing technique to small pelvis with a 12 cm x 12 cm treatment field (44-45 Gy) combined with conformation radiotherapy to prostate (20-26 Gy). Chemotherapy was performed using either one or a combination of the following; cis-diamminedichloroplatinum, adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate and etoposide. The observation period was 54.5 months on the average. Recurrence was observed in 3 patients, for all of which the sites were at bone. The 5-year non-recurrence rate was 90.4% by Kaplan-Meier's method. There were 4 deaths, three were due to prostate cancer and one to gastric cancer. The 5-year cumulative survival rate by Kaplan-Meier's method was 90.5%. In conclusion, this treatment was effective for stage C cases of prostate cancer. (author)

Combination of chemotherapy and heavy-ion particle therapy for pancreas cancer

International Nuclear Information System (INIS)

Yamada, Shigeru; Ando, Koichi

2003-01-01

The purpose of this study is to investigate the combination of chemotherapy and heavy-ion particle therapy for pancreas cancer. We measured surviving fractions in four culture pancreas cancer cells. The cell killing of heavy-ion irradiation is more effective compared to that of X ray irradiation. Gemcitabine induced radiosensitization for pancreas cancer cells. (author)

Combination of chemotherapy and heavy-ion particle therapy for pancreas cancer

International Nuclear Information System (INIS)

Yamada, Shigeru; Ando, Koichi

2004-01-01

The purpose of this study is to investigate the combination of chemotherapy and heavy-ion particle therapy for pancreas cancer. We measured surviving fractions in four culture pancreas cancer cells. The cell killing of heavy-ion irradiation is more effective compared to that of X ray irradiation. Gemcitabine induced radiosensitization for pancreas cancer cells. (author)

Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naïve with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE))

Science.gov (United States)

Emery, P; Deodhar, A; Rigby, W F; Isaacs, J D; Combe, B; Racewicz, A J; Latinis, K; Abud-Mendoza, C; Szczepański, L J; Roschmann, R A; Chen, A; Armstrong, G K; Douglass, W; Tyrrell, H

2010-01-01

Objectives This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. Methods Patients with active disease on stable MTX (10–25 mg/week) were randomised to rituximab 2×500 mg (n=168), rituximab 2×1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) ≥2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2×500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. Results At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2×500 mg) + MTX, rituximab (2×1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. Conclusions Rituximab (at 2×500 mg and 2×1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses. PMID:20488885

Chemotherapy by superselective intraarterial infusion of nedaplatin combined with radiotherapy for oral cancer

International Nuclear Information System (INIS)

Yamashita, Yoshio; Goto, Masaaki; Katsuki, Takeshi

2002-01-01

Nedaplatin (CDGP), which is a CDDP derivative, has been reported to be an effective anticancer agent for head and neck cancer. This study was performed to assess the feasibility of chemotherapy by superselective intraarterial infusion of nedaplatin (CDGP) in patients with oral cancers. Ten patients were treated with chemotherapy by superselective intraarterial infusion of CDGP combined with radiotherapy. The complete and partial response rates were 7/10 (70%) and 3/10 (30%), respectively. Nine patients showed grade 1-2 hematological toxicity including leukocytopenia and anemia. Thrombocytopenia of grade 4 was seen in only one patient. However, all the patients were free from renal dysfunction. From these results, it is suggested that this combination therapy might be quite effective and safe. Further study will be needed to determine its efficacy against oral cancer. (author)

Chemotherapy by superselective intraarterial infusion of nedaplatin combined with radiotherapy for oral cancer

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Yamashita, Yoshio; Goto, Masaaki; Katsuki, Takeshi [Saga Medical School (Japan)

2002-06-01

Nedaplatin (CDGP), which is a CDDP derivative, has been reported to be an effective anticancer agent for head and neck cancer. This study was performed to assess the feasibility of chemotherapy by superselective intraarterial infusion of nedaplatin (CDGP) in patients with oral cancers. Ten patients were treated with chemotherapy by superselective intraarterial infusion of CDGP combined with radiotherapy. The complete and partial response rates were 7/10 (70%) and 3/10 (30%), respectively. Nine patients showed grade 1-2 hematological toxicity including leukocytopenia and anemia. Thrombocytopenia of grade 4 was seen in only one patient. However, all the patients were free from renal dysfunction. From these results, it is suggested that this combination therapy might be quite effective and safe. Further study will be needed to determine its efficacy against oral cancer. (author)

Combination of radiotherapy and selective chemotherapy in the treatment of advanced ovarian carcinomas

International Nuclear Information System (INIS)

Dietz, R.; Brachetti, A.; Universitaet des Saarlandes, Homburg/Saar

1982-01-01

A report is given on 160 patients suffering from ovarian carcinomas the stages which were exactly determined by TNM classification. 32 patients had tumors of the stages T1-T3, 128 patients had tumors of the stage T4. All T3 subgroups showed favorable results after radical surgery and a postoperative combination of radiotherapy and selective cytostatic chemotherapy. The therapy plans including radiotherapy had more advantages than those without radiotherapy. Furthermore, the cytostatic treatment was more successful after a chemotherapy resistance test than after blind administration of cytostatic drugs. (orig.) [de

The Efficacy of Synchronous Combination of Chemotherapy and EGFR TKIs for the First-Line Treatment of NSCLC: A Systematic Analysis.

Directory of Open Access Journals (Sweden)

Han Yan

Full Text Available The combination of chemotherapy and epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs currently has become the hotspot issue in the treatment of non-small lung cancer (NSCLC. This systematic review was conducted to compare the efficacy and safety of the synchronous combination of these two treatments with EGFR TKIs or chemotherapy alone in advanced NSCLC.EMBASE, PubMed, the Central Registry of Controlled Trials in the Cochrane Library (CENTRAL, Chinese biomedical literature database (CNKI and meeting summaries were searched. The Phase II/III randomized controlled trials were selected by which patients with advanced NSCLC were randomized to receive a combination of EGFR TKIs and chemotherapy by synchronous mode vs. EGFR TKIs or chemotherapy alone.A total of six randomized controlled trials (RCTs including 4675 patients were enrolled in the systematic review. The meta-analysis demonstrated that the synchronous combination group of chemotherapy and EGFR TKIs did not reach satisfactory results; there was no significant difference in overall survival (OS, time to progression (TTP and objective response rate (ORR, compared with monotherapy (OS: HR = 1.05, 95%CI = 0.98-1.12; TTP: HR = 0.94, 95%CI = 0.89-1.00; ORR: RR = 1.07, 95%CI = 0.98-1.17, and no significant difference in OS and progression-free survival (PFS, compared with EGFR TKIs alone (OS: HR = 1.10, 95% CI = 0.83-1.46; PFS: HR = 0.86, 95% CI = 0.67-1.10. The patients who received synchronous combined therapy presented with increased incidences of grade 3/4 anemia (RR = 1.40, 95% CI = 1.10-1.79 and rash (RR = 7.43, 95% CI = 4.56-12.09, compared with chemotherapy, grade 3/4 anemia (RR = 6.71, 95% CI = 1.25-35.93 and fatigue (RR = 9.60, 95% CI = 2.28-40.86 compared with EGFR TKI monotherapy.The synchronous combination of chemotherapy and TKIs is not superior to chemotherapy or EGFR TKIs alone for the first-line treatment of NSCLC.

Retrospective analysis of rituximab therapy and splenectomy in childhood chronic and refractory immune thrombocytopenic purpura.

Science.gov (United States)

Ay, Yilmaz; Karapinar, Tuba H; Oymak, Yesim; Toret, Ersin; Demirag, Bengu; Ince, Dilek; Ozcan, Esin; Moueminoglou, Nergial; Koker, Sultan A; Vergin, Canan

2016-06-01

Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively.None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab.

99mTc-rituximab radiolabelled by photo-activation: a new non-Hodgkin's lymphoma imaging agent

International Nuclear Information System (INIS)

Gmeiner Stopar, T.; Fettich, J.; Hojker, S.; Mlinaric-Rascan, I.; Mather, S.J.

2006-01-01

Rituximab was the first chimeric monoclonal antibody to be approved for treatment of indolent B-cell non-Hodgkin's lymphoma (NHL). It is directed against the CD20 antigen, which is expressed by 95% of B-cell NHLs. The aim of this study was to explore the possibility of radiolabelling rituximab with 99m Tc for use as an imaging agent in NHL for early detection, staging, remission assessment, monitoring for metastatic spread and tumour recurrence, and assessment of CD20 expression prior to (radio)immunotherapy. Rituximab was purified from Mabthera solution (Roche), photo-activated at 302 nm by UV irradiation and radiolabelled with 99m Tc. The effectiveness of the labelling method was evaluated by determination of the number of free thiol groups per photoreduced antibody, radiochemical purity and in vitro stability of 99m Tc-rituximab. On average, 4.4 free thiol groups per photoreduced antibody were determined. Radiolabelling yields greater than 95% were routinely observed after storage of the photo-activated antibody at -80 C for 195 days. The direct binding assay showed preserved ability of 99m Tc-rituximab to bind to CD20, with an average immunoreactive fraction of 93.3%. The internalisation rate was proven to be low, with only 5.3% of bound 99m Tc-rituximab being internalised over 4 h at 37 C. Our results demonstrate that 99m Tc-rituximab of high radiochemical purity and with preserved binding affinity for the antigen can be prepared by photoreduction and that the method shows good reproducibility. 99m Tc-rituximab will be further explored as an imaging agent applicable in NHL for the purposes mentioned above. (orig.)

RITUXIMAB: NEW POTENTIALITIES OF THERAPY FOR RHEUMATOID ARTHRITIS

Directory of Open Access Journals (Sweden)

D E Karateev

2008-01-01

Full Text Available Some patients with rheumatoid arthritis (RA are unresponsive or intolerant to both synthetic first-line anti-inflammatory drugs (FLAID and tumor necrosis factor (TNF а inhibitors already included into all the treatment standards . Along with the conventional methods for overcoming drug resistance - switching to another FLAID or another TNF а blocker, the use of biologicals with another mechanism of action rather than suppression of TNF а gives a good account of itself. Prominent among these agents is the anti-B-cell drug rituximab. The new possibilities of the therapy, which open up the use of rituximab in patients with RA, are discussed.

Combination of chemotherapy, radiotherapy and surgery in the treatment of oral cancer

International Nuclear Information System (INIS)

Ayyagiri, S.; Gupta, B.D.; Dutta, T.K.

1980-01-01

In locally advanced oral cancer, the main modalities of treatment, e.g. surgery and radiotherapy, most often fail to control the disease when used singly. A combination policy of surgery and radiotherapy achieves adequate control of the disease. In order to improve the results in advanced oral cancer, chemotherapy given prior to and during radiation treatment and judicious combination of surgery offer the best possible approach in the management. The experience in the combination policy in the treatment of oral cancer in Northern India is dealt with. (auth.)

Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab.

Science.gov (United States)

Theodore-Oklota, Christina; Humphrey, Louise; Wiesner, Christof; Schnetzler, Gabriel; Hudgens, Stacie; Campbell, Alicyn

2016-01-01

A subcutaneous (SC) formulation of rituximab (MabThera ® /Rituxan ® ) has been developed that could reduce administration time and improve patient satisfaction with treatment. The Rituximab Administration Satisfaction Questionnaire (RASQ) was created to assess patients' perceptions and satisfaction with rituximab SC (RASQ-SC) or rituximab intravenous (RASQ-IV). We assessed the content validity and psychometric properties of RASQ in patients with non-Hodgkin lymphoma. Face and content validity of RASQ-SC and RASQ-IV were qualitatively assessed using 60-minute combined concept elicitation and cognitive debriefing interviews. Psychometric validation of RASQ (item performance and reliability) was assessed quantitatively against the established Cancer Therapy Satisfaction Questionnaire (CTSQ), using questionnaire data from the PrefMab (NCT01724021) and MabCute (NCT01461928) clinical studies. RASQ-IV demonstrated excellent coverage of concepts relevant to patients' (n=10) own treatment experiences and no new concepts were identified. Patients' expectations of rituximab SC were conceptually consistent with items included in the RASQ-SC, suggesting that the tool is also conceptually adequate. In 1,051 patients from PrefMab and MabCute, correlations with domains such as "RASQ: Physical Impacts" and "CTSQ: Feelings About Side Effects", "RASQ: Physical Impacts" and "CTSQ: Satisfaction With Therapy", and "RASQ: Satisfaction" and "CTSQ: Satisfaction With Therapy", achieved moderate-to-high correlations (>0.4) for convergent domains and <0.3 for divergent domains. This study supports the qualitative face and content validity and psychometric validity of RASQ-IV and RASQ-SC. Minor revisions were made to the questionnaires to enhance clarity and aid consistent reporting.

Malignant Esophagogastric Junction Obstruction: Efficacy of Balloon Dilation Combined with Chemotherapy and/or Radiation Therapy

International Nuclear Information System (INIS)

Ko, Gi-Young; Song, Ho-Young; Hong, Heuk-Jin; Sung, Kyu-Bo; Seo, Tae-Seok; Yoon, Hyun-Ki

2003-01-01

Purpose: To assess the efficacy of balloon dilation combined with chemotherapy and/or radiation therapy for palliation of dysphagia due to malignant esophagogastric junction strictures. Methods: Fluoroscopically guided balloon dilation was attempted in 20 patients. The causes of strictures were gastric adenocarcinoma (n = 10) and esophageal squamous cell carcinoma (n = 10). Scheduled chemotherapy and/or radiation therapy followed balloon dilation in all patients. Results: There were no technical failures or major complications. After balloon dilation, 15 (75%) patients showed improvement of dysphagia. No patient complained of reflux esophagitis during the follow-up period. Among the 15 patients, seven needed no further treatment for palliation of dysphagia until their deaths. The remaining eight patients underwent repeat balloon dilation(n = 4) or stent placement (n = 4)3-43 weeks (mean 15 weeks) after the initial balloon dilation because of recurrent dysphagia. Conclusion: Balloon dilation combined with chemotherapy and/or radiation therapy seems to be an easy and reasonably effective palliative treatment for malignant esophagogastric strictures

Low dose combined chemotherapy/radiotherapy in the management of locally advanced urethral squamous cell carcinoma

International Nuclear Information System (INIS)

Johnson, D.W.; Kessler, J.F.; Ferrigni, R.G.; Anderson, J.D.

1989-01-01

The successful treatment of a patient with bulky squamous cell carcinoma of the urethra using low dose preoperative radiation therapy and concurrent chemotherapy is described. Dramatic rapid tumor response facilitated surgical resection of the remaining microscopic disease. This clinical behavior is remarkably similar to that seen with squamous cell carcinoma of the anal canal and esophagus when a similar regimen is used. At the latter tumor sites the successful use of combination radiotherapy and chemotherapy has reduced the morbidity of subsequent surgery, and in selected cases has obviated the need for a radical operation. Further investigation of such combination treatment is warranted for urethral carcinoma

Rituximab treatment in primary angiitis of the central nervous system.

Science.gov (United States)

Patel, Shreeya; Ross, Laura; Oon, Shereen; Nikpour, Mandana

2018-06-01

Primary angiitis of the central nervous system (PACNS) is a rare autoimmune vasculitis affecting the brain and spinal cord. Treatment with biological agents has revolutionised the treatment of many rheumatic conditions but there is scant literature regarding the use of biological agents in PACNS. We present three cases of PACNS treated with rituximab, including two cases of relapsed disease, and a literature review suggesting a role for rituximab in this condition. © 2018 Royal Australasian College of Physicians.

Fulminante, rituximab-resistente, mucocutane pemphigus vulgaris

NARCIS (Netherlands)

Gostyński, A.; Ammatuna, E.; Huls, G.; Wouthuyzen-Bakker, M.; Jonkman, M. F.; Horváth, B.

2017-01-01

Pemphigus vulgaris is an autoimmune disease mediated by auto-antibodies against desmoglein 1 and 3. First line treatment for pemphigus consists of systemic corticosteroids and anti-CD20 therapy (rituximab) to eliminate B-cells. Since 2005, more than 100 patients with pemphigus have been treated with

Hepatitis B reactivation and rituximab: a new boxed warning and considerations for solid organ transplantation.

Science.gov (United States)

Martin, S T; Cardwell, S M; Nailor, M D; Gabardi, S

2014-04-01

Use of rituximab, a chimeric monoclonal antibody directed at the CD20 antigen, continues to increase in solid organ transplantation (SOT) for several off-label uses. In September 2013, the United States Food and Drug Administration (FDA) issued a Drug Safety Communication to oncology, rheumatology and pharmacy communities outlining a new Boxed Warning for rituximab. Citing 109 cases of fatal hepatitis B virus (HBV) reactivation in persons receiving rituximab therapy with previous or chronic HBV infection documented in their Adverse Event Reporting System (AERS), the FDA recommends screening for HBV serologies in all patients planned to receive rituximab and antiviral prophylaxis in any patient with a positive history of HBV infection. There is a lack of data pertaining to this topic in the SOT population despite an increase in off-label indications. Previous reports suggest patients receiving rituximab, on average, were administered six doses prior to HBV reactivation. Recommendations on prophylaxis, treatment and re-challenging patients with therapy after resolution of reactivation remain unclear. Based on data from the FDA AERS and multiple analyses in oncology, SOT providers utilizing rituximab should adhere to the FDA warnings and recommendations regarding HBV reactivation until further data are available in the SOT population. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Micro-costing study of rituximab subcutaneous injection versus intravenous infusion in dutch setting

NARCIS (Netherlands)

Mihajlović, J.; Bax, P.; Van Breugel, E.; Blommestein, H.M.; Hoogendoorn, M.; Hospes, W.; Postma, M.J.

2015-01-01

Background: Rituximab for subcutaneous (SC) administration has recently been approved for use in common forms of diffuse large B-cell lymphoma (DLBCL). This form of rituximab is supplied in ready-to-use vials that do not require individual dose adjustment. It is expected that SC-injection will

Early plasmapheresis and rituximab for acute humoral rejection after ABO-compatible liver transplantation

Institute of Scientific and Technical Information of China (English)

Nassim Kamar; Laurence Lavayssière; Fabrice Muscari; Janick Selves; Céline Guilbeau-Frugier; Isabelle Cardeau; Laure Esposito; Olivier Cointault; Marie Béatrice Nogier; Jean Marie Peron; Philippe Otal; Marylise Fort; Lionel Rostaing

2009-01-01

Acute humoral rejection (AHR) is uncommon after ABOcompatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Liver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab.Liver enzymes returned to within normal range 18 dafter diagnosis. Liver biopsies, at 3 and 9 mo post-transplant,showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.

Combination of chemotherapy and heavy-ion particle therapy for gastrointestinal cancer

International Nuclear Information System (INIS)

Yamada, Shigeru; Kitabayashi, Hiroyuki; Furusawa, Yoshiya; Ando, Koichi

2005-01-01

The purpose of this study is to investigate the combination of chemotherapy and heavy-ion particle therapy for pancreas and esophageal cancer. We measured surviving fractions in four culture pancreas and esophageal cancer cells. The cell killing of heavy-ion irradiation is more effective compared to that of X ray irradiation. Gemcitabine induced radiosensitization for pancreas cancer cells and also taxotel for esophageal cancer. (author)

Analytical similarity assessment of rituximab biosimilar CT-P10 to reference medicinal product.

Science.gov (United States)

Lee, Kyoung Hoon; Lee, Jihun; Bae, Jin Soo; Kim, Yeon Jung; Kang, Hyun Ah; Kim, Sung Hwan; Lee, So Jung; Lim, Ki Jung; Lee, Jung Woo; Jung, Soon Kwan; Chang, Shin Jae

2018-04-01

CT-P10 (Truxima™) was recently approved as the world's first rituximab biosimilar product in the European Union (EU) and South Korea. To demonstrate biosimilarity of CT-P10 with the reference medicinal product (RMP), extensive 3-way similarity assessment has been conducted between CT-P10, EU-Rituximab and US-Rituximab, focusing on the physicochemical and biological quality attributes. A multitude of state-of-the-art analyses revealed that CT-P10 has identical primary and higher order structures compared to the original product. Purity/impurity profiles of CT-P10 measured by the levels of aggregates, fragments, non-glycosylated form and process-related impurities were also found to be comparable with those of RMPs. In terms of the post-translational modification, CT-P10 contains slightly less N-terminal pyro-glutamate variant, which has been known not to affect product efficacy or safety. Oligosaccharide profiling has revealed that, although CT-P10 contains the same conserved glycan species and relative proportion with the RMPs, the content of total afucosylated glycan in CT-P10 was slightly higher than in EU- or US-Rituximab. Nevertheless, the effect of the observed level of afucosylation in CT-P10 drug product on Fc receptor binding affinity or antibody-dependent cell-mediated cytotoxicity was found to be negligible based on the spiking study with highly afucosylated sample. Arrays of biological assays representative of known and putative mechanisms of action for rituximab have shown that biological activities of CT-P10 are within the quality range of RMPs. Recent results of clinical studies have further confirmed that the CT-P10 exhibits equivalent clinical efficacy and safety profiles compared to EU- and US-Rituximab. The current 3-way similarity assessment together with clinical study results confidently demonstrate that CT-P10 is highly similar with EU- and US-Rituximab in terms of physicochemical properties, biological activities, efficacy, and safety for

Transarterial infusion chemotherapy combined with high intensity focused ultrasound for the treatment of pancreatic carcinomas: a clinical study

International Nuclear Information System (INIS)

Zhang Yiping; Zhao Jingzhi; Qiao Xinrong; Huang Hankui

2011-01-01

Objective: To assess the clinical value of transarterial infusion chemotherapy combined with high intensity focused ultrasound (HIFU) for the treatment of pancreatic carcinomas. Methods: A total of 64 patients with inoperable pancreatic carcinomas were randomly divided into study group (n=32) and control group (n=32). Transarterial infusion chemotherapy combined with HIFU was employed in patients of study group, while simple transarterial infusion chemotherapy was conducted in patients of control group. The effective rate, the clinical benefit rate (CBR), the occurrence of side effect and the survival time of the two groups were recorded. The results were compared between the two groups. Results: The effective rate (PR + MR), the median survival time and the one-year survival rate of the study group were 55.56%, 13.0 months and 68.75% respectively, while the effective rate (PR + MR), the median survival time and the one-year survival rate of the control group were 28.57%, 9.0 months and 43.75% respectively. Both the effective rate and the one-year survival rate of the study group were significantly higher than those of the control group (P<0.05). Conclusion: Compared with pure transarterial infusion chemotherapy, transarterial infusion chemotherapy combined with HIFU can significantly improve the short-term efficacy and increase the one-year survival rate for patients with advanced pancreatic carcinomas. (authors)

Meta-analysis of gemcitabine and cisplatin combination chemotherapy versus gemcitabine alone for pancreatic cancer

Directory of Open Access Journals (Sweden)

Diyu Huang

2016-01-01

Conclusions: Overall response rate, stable disease, and progressive disease, as well as 1-year survival rate in patients who received GEM + CIS, were superior to those treated with GEM alone. Combination chemotherapy with GEM and CIS may offer greater benefits in the treatment of pancreatic cancer than that of GEM alone although the combination group had higher hematological toxicities.

Long-term safety of rituximab induced peripheral B-cell depletion in autoimmune neurological diseases.

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Anza B Memon

Full Text Available B-cells play a pivotal role in several autoimmune diseases, including patients with immune-mediated neurological disorders (PIMND, such as neuromyelitis optica (NMO, multiple sclerosis (MS, and myasthenia gravis (MG. Targeting B-cells has been an effective approach in ameliorating both central and peripheral autoimmune diseases. However, there is a paucity of literature on the safety of continuous B-cell depletion over a long period of time.The aim of this study was to examine the long-term safety, incidence of infections, and malignancies in subjects receiving continuous therapy with a B-cell depleting agent rituximab over at least 3 years or longer.This was a retrospective study involving PIMND who received continuous cycles of rituximab infusions every 6 to 9 months for up to 7 years. The incidence of infection related adverse events (AE, serious adverse events (SAE, and malignancies were observed.There were a total of 32 AE and 4 SAE with rituximab treatment. The 3 SAE were noted after 9 cycles (48 months and 1 SAE was observed after 11 cycles (60 months of rituximab. There were no cases of Progressive multifocal leukoencephalopathy (PML and malignancies observed throughout the treatment period. Rituximab was well tolerated without any serious infusion reactions. Also, rituximab was found to be beneficial in treating PIMND over a 7-year period.This study demonstrates that long-term depletion of peripheral B-cells appears safe and efficacious in treating PIMND. Longer and larger prospective studies with rituximab are needed to carefully ascertain risks associated with chronic B-cell depletion, including malignancies. Recognizing that this is a small, retrospective study, such data nonetheless complement the growing literature documenting the safety and tolerability of B-cell depleting agents in neurological diseases.

Individualized rituximab treatment for relapsing neuromyelitis optica: a pediatric case report.

Science.gov (United States)

He, Dian; Yu, YunLi; Yan, WeiBo; Dai, QingQing; Xu, Zhu; Chu, Lan

2014-08-01

Neuromyelitis optica is an autoimmune inflammatory disorder of the central nervous system. Current therapeutic approaches are based on small uncontrolled trials, case series, or case reports. There are only a few case reports describing rituximab for pediatric neuromyelitis optica. A 7-year-old girl with neuromyelitis optica had high disease activity with recurrent myelitis and steroid dependence. A remarkable increase of CD19(+) B-cell count in the peripheral blood mononuclear cells and seropositivity for anti-aquaporin 4 antibody were detected at each attack. After induction therapy with rituximab, the CD19(+) B-cell number was significantly reduced and sustained at low levels. The level of serum anti-aquaporin 4 antibody normalized. She was relapse-free over 1-year follow-up period. An individualized maintenance therapy scheme is underway. Treatment with rituximab for relapsing neuromyelitis optica requires an individualized regimen to optimize the frequency and dosage of administration to maximize efficacy yet minimize overtreatment and cost. Personal levels of CD19(+) B cells in peripheral blood mononuclear cells at previous attacks and responsiveness to rituximab in induction therapy may be two useful indicators in establishing individualized maintenance therapy schemes for relapsing neuromyelitis optica. Copyright © 2014 Elsevier Inc. All rights reserved.

Jianpi Bushen, a Traditional Chinese Medicine Therapy, Combined with Chemotherapy for Gastric Cancer Treatment: A Meta-Analysis of Randomized Controlled Trials

Science.gov (United States)

Chen, Yunbo; Zhang, Guijuan; Chen, Xiaoping; Jiang, Xuefeng; Yuan, Naijun; Wang, Yurong; Hao, Xiaoqian

2018-01-01

Objective. To investigate the effects of Jianpi Bushen (JPBS), a traditional Chinese medicine that is used to invigorate the spleen and tonify the kidney, combined with chemotherapy for the treatment of gastric cancer. Methods. Literature retrieval was performed in PubMed, EMBASE, Cochrane Library, MEDLINE, CNKI, Wanfang Data Information Site, and VIP from inception to October 2017. Randomized controlled trials to evaluate the effects of JPBS combined with chemotherapy were identified. The primary reported outcomes were KPS (Karnofsky Performance Status), clinical curative efficiency, immune function, blood system, and nonhematologic system. Review Manager 5.3 (RevMan 5.3) was used for data analysis, and the quality of the studies was also appraised. Results. A total of 26 studies were included with 3098 individuals. The results of the meta-analysis indicated that treatment of gastric cancer with the combination of JPBS and chemotherapy resulted in better outcomes compared to chemotherapy alone. Conclusion. Evidence from the meta-analysis suggested that JPBS combined with chemotherapy has a positive effect on gastric cancer treatment. However, additional rigorously designed and large sample randomized controlled trials are required to confirm the efficacy and safety of this treatment. PMID:29675052

Comparative analyses of the effect of radiotherapy and chemotherapy or chemotherapy alone on patients' electrocardiogram

International Nuclear Information System (INIS)

Liang Li; Zhang Shulan; Zhang Zhaohui; Wang Junjie; Jia Tingzhen

2005-01-01

Objective: To investigate the change of breast cancer patients' electrocardiogram during combined radiotherapy and chemotherapy or chemotherapy alone for the sake of predicting the cardiotoxicity of combined radiotherapy and chemotherapy. Methods: From January, 1998 to June, 2004, 47 postoperative breast cancer patients were enrolled. Among them 29 patients received chemotherapy combined with radiotherapy (combinative group), and 18 patients received chemotherapy alone (non combinative group). The changes of electrocardiogram were observed and correlation factors were analyzed. Results: Abnormal electrocardiograms were noted in 11 (37.9%) and 2 patients (11.1%) of the combinative group and the non-combinative group respectively(z=-1.977, P=0.048). In the combinative group, heart events were significantly increased in patients above 60 years old (z=- 2.094 P=0.036). The changes of electrocardiogram were not significantly correlative with hypertension history, tumor site, dose of radiotherapy or chemotherapeutic drugs. But the incidence of abnormal electrocardiogram was higher in patients with a hypertension history than in those without it (54.5% vs 27.8%). Conclusion: The abnormalities of electrocardiogram were are more frequent in patients treated with both radiotherapy combined with chemotherapy. Our results suggest that breast cancer patients should be regularly reexamined with electrocardiography during therapy, especially whose age was those have a hypertension history and above 60 years old. (authors)

Induction chemotherapy combined with three-dimensional conformal radiation therapy for locally advanced non-small cell lung cancer

International Nuclear Information System (INIS)

Zheng Aiqing; Yu Jinming; Zhao Xianguang; Wang Xuetao; Wei Guangsheng

2005-01-01

Objective: To evaluate the effect and complication of induction chemotherapy combined with three-dimensional conformal radiation therapy (3DCRT) for locally advanced non small cell lung cancer (NSCLC). Methods: Ninety-two such patients were randomized into radiation therapy alone group(RT-, 50 patients) and induction chemotherapy combined radiotherapy group (CMT-, 42 patients). The induction chemotherapy consisted of 2-4 cycles of platinum-based regimen. Results: The overall median survival time was 15 months with 12 months in the RT group and 18 months in the CMT group (P=0.014) respectively. The 1-year overall survival rates were 48.6% and 71.2% in RT and CMT group, respectively (P=0.004). The 2-year survival rates were 20.8% and 37.6% in RT and CMT group, respectively (P=0.041). Treatment was well tolerated and the toxicities were similar in either group. Conclusion: The addition of induction chemotherapy to 3DCRT takes a survival advantage over 3DCRT alone for Stage III NSCLC without increasing toxicities. (authors)

Combined chemotherapy and radiotherapy in recurrent tumors of the head and neck region

International Nuclear Information System (INIS)

Tsuji, Hiroshi; Tsujii, Hirohiko; Kamada, Tadashi; Takamura, Akio; Shirato, Hiroki; Matsuoka, Yoshisuke; Irie, Goro

1987-01-01

Over the past four years, 27 patients with recurrent tumors of the head and neck region have been treated with chemotherapy. The regimens used were BCMF (bleomycin 15 mg i.v. for 3 days, cyclophosphamide 500 mg i.v., methotrexate 50 mg i.v. and 5-fluorouracil 500 mg i.v.) and CMU (cyclophosphamide 350 mg/m 2 i.v., methotrexate 30 mg/m 2 i.v. and UFT 600 mg p.o. for 14 days). Of the 27 patients, eight were treated with combined radiation and chemotherapy, and either CR or PR was obtained. Nineteen patients were treated with chemotherapy alone, for which the response (CR + PR) rates were 8 % (1/12) for BCMF and 43 % (3/7) for CMU, respectively. No serious toxicities were observed as a result of these regimens. It was thus demonstrated that the CMU regimen was of great value in terms of improved response and minor toxicity in the treatment of head and neck tumors. (author)

Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer

DEFF Research Database (Denmark)

Joensuu, H; Holli, K; Heikkinen, M

1998-01-01

PURPOSE: We report results of a randomized prospective study that compared single agents of low toxicity given both as the first-line and second-line chemotherapy with combination chemotherapy in advanced breast cancer with distant metastases. PATIENTS AND METHODS: Patients in the single-agent arm...... (n = 153) received weekly epirubicin (E) 20 mg/m2 until progression or until the cumulative dose of 1,000 mg/m2, followed by mitomycin (M) 8 mg/m2 every 4 weeks, and those in the combination chemotherapy arm (n = 150) were first given cyclophosphamide 500 mg/m2, E 60 mg/m2, and fluorouracil 500 mg/m2...... younger than 50. RESULTS: An objective response (complete [CR] or partial [PR]) was obtained in 55%, 48%, 16%, and 7% of patients treated with CEF, E, M, and MV, respectively. A response to CEF tended to last longer than a response to E (median, 12 v 10.5 months; P = .07). Treatment-related toxicity...

Favourable response to rituximab by an ocular adnexal primary lymphoma.

Science.gov (United States)

Luque Valentin-Fernandez, M L; Alvarez Rodríguez, F; Rodríguez Jiménez, I

2016-11-01

A 70-year-old woman who presented with an extranodal marginal zone B-cell lymphoma in lacrimal gland and conjunctiva. Initial treatment with rituximab yielded an immediate good response. Five months later she showed lymphoid proliferation in her contralateral conjunctiva. Although no additional treatment was performed, the patient has been free of systemic symptoms and recurrences. Rituximab is a quite good therapeutic agent in low grade adnexal lymphomas. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Imaging and measuring the rituximab-induced changes of mechanical properties in B-lymphoma cells using atomic force microscopy

Energy Technology Data Exchange (ETDEWEB)

Li, Mi [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Liu, Lianqing, E-mail: lqliu@sia.cn [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Xi, Ning, E-mail: xin@egr.msu.edu [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Department of Electrical and Computer Engineering, Michigan State University, East Lansing, MI 48824 (United States); Wang, Yuechao; Dong, Zaili [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Tabata, Osamu [Department of Micro Engineering, Kyoto University, Kyoto 606-8501 (Japan); Xiao, Xiubin [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China); Zhang, Weijing, E-mail: zhangwj3072@163.com [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China)

2011-01-14

Research highlights: {yields} Single B-lymphoma living cells were imaged by AFM with the assistance of microfabricated pillars. {yields} The apoptosis of B-lymphoma cells triggered by rituximab without cross-linking was observed by AO/EB double fluorescent staining. {yields} The B-lymphoma cells became dramatically softer after adding rituximab. -- Abstract: The topography and mechanical properties of single B-lymphoma cells have been investigated by atomic force microscopy (AFM). With the assistance of microfabricated patterned pillars, the surface topography and ultrastructure of single living B-lymphoma cell were visualized by AFM. The apoptosis of B-lymphoma cells induced by rituximab alone was observed by acridine orange/ethidium bromide (AO/EB) double fluorescent staining. The rituximab-induced changes of mechanical properties in B-lymphoma cells were measured dynamically and the results showed that B-lymphoma cells became dramatically softer after incubation with rituximab. These results can improve our understanding of rituximab'effect and will facilitate the further investigation of the underlying mechanisms.

Metronomic Cyclophosphamide and Methotrexate Chemotherapy Combined with 1E10 Anti-Idiotype Vaccine in Metastatic Breast Cancer

International Nuclear Information System (INIS)

Soriano, J.L.; Batista, N.; Lima, M.; Gonzalez, J.; Garcia, R.; Zarza, Y.; Lopez, M.V.; Rodriguez, M.; Loys, J.L.; Montejo, N.; Santiesteban, E.; Aguirre, F.; Macias, A.; Vazquez, A.M.

2011-01-01

The use of low doses of cytotoxic agents continuously for prolonged periods is an alternative for the treatment of patients with metastatic breast cancer who have developed resistance to conventional chemotherapy. The combination of metronomic chemotherapy with therapeutic vaccines might increase the efficacy of the treatment. Twenty one patients with metastatic breast cancer in progression and a Karnosky index =60%, were treated with metronomic chemotherapy (50?mg of cyclophosphamide orally daily and 2.5 mg of methotrexate orally bi-daily), in combination with five bi-weekly subcutaneous injections of 1 mg of aluminum hydroxide-precipitated 1E10 anti-idiotype MAb (1E10-Alum), followed by re immunizations every 28 days. Five patients achieved objective response, eight showed stable disease and eight had disease progression. Median time to progression was 9,8 months, while median overall survival time was 12,93 months. The median duration of the response (CR+PR+SD) was 18,43 months (12,20-24,10 months), being higher than 12 months in 76,9% of the patients. Overall toxicity was generally mild. Metronomic chemotherapy combined with 1E10-Alum vaccine immunotherapy might be a useful therapeutic option for the treatment of metastatic breast cancer due to its potential impact on survival and patient quality of live, low toxicity and advantages of the administration.

Combination chemotherapy concurrent with small dose radiation therapy for small cell carcinoma of the lung

International Nuclear Information System (INIS)

Tada, Toshihiko; Fujita, Hiroji; Shintomi, Takenori

1987-01-01

Forty consecutive patients with small cell carcinoma of the lung were treated with chemotherapy, radiotherapy or both. Of 34 patients treated with chemotherapy, 24 were treated with combination chemotherapy, containing cyclophosphamide vincristine methotrexate and procarbazine, concurrent with small dose radiation therapy (500 cGy/5 fraction) as a chemosensitizer (COMPrt). The response rate to this regimen was 81 % (29 % complete) and the 2 year survival rate was 28.6 %. These results have been superior to other regimens and the toxicity was not see to be any higher. After completion of COMPrt regimen, 10 patients were treated with intrathoracic radiation therapy (average dose 3000 cGy) and 3 recieved surgical treatment. Radiation therapy improved the 2-year survival rate (42.2 %) when compared with those patients who received no radiation therapy (18.2 %). Three patients received surgical treatment were considered to be disease-free for 23, 17, and 9 months respectively, after induction of chemotherapy. (author)

Transarterial infusion chemotherapy with a combination of gemcitabine and 5-fluorouracil in advanced pancreatic carcinoma

International Nuclear Information System (INIS)

Shi Haifeng; Jin Zhengyu; Yang Ning; Liu Wei; Pan Jie; Cai Lixing; Zhao Yupei; Zhou Zhiqiang

2002-01-01

Objective: To retrospectively analyze the effectiveness of transarterial infusion chemotherapy of gemcitabine and 5-fluorouracil in advanced pancreatic carcinoma. Methods: Twenty-two patients with advanced pancreatic carcinoma were treated with transarterial infusion chemotherapy. Gemcitabine and 5-fluorouracil was administered to the patients via an interarterial catheter. Then the tumor response rate and clinical benefit were observed. Results: A clinical benefit was obtained in 8 patients (36.4%). The tumor response rate was 13.6%. Median survival for all the patients was 6.1 months. Median time to tumor progression was 2.9 months. Conclusion: Transarterial infusion chemotherapy with a combination of gemcitabine and 5-fluorouracil appears to have good clinical benefit and may prolong the survival time of patients with advanced pancreatic carcinoma

A Case of Rituximab-Induced Necrotizing Fasciitis and a Review of the Literature

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Abdullateef Abdulkareem

2017-01-01

Full Text Available Necrotizing fasciitis is a fulminant soft tissue infection characterized by rapid progression and high mortality. Rituximab is a generally well-tolerated immunosuppresive medication used for B-cell malignancies and some rheumatological disorders. We report a case of a 69-year-old male with chronic lymphocytic leukemia who suffered necrotizing fasciitis of his left lower extremity secondary to Clostridium septicum 7 weeks after treatment with rituximab. Despite immediate intravenous antimicrobial therapy and emergent fasciotomy with extensive debridement, his hospital course was complicated by septic shock and he required an above-the-knee amputation. Physicians need to be aware of the possibility of necrotizing fasciitis in patients presenting with skin infections after rituximab therapy.

A Case of Rituximab-Induced Necrotizing Fasciitis and a Review of the Literature.

Science.gov (United States)

Abdulkareem, Abdullateef; D'Souza, Ryan S; Shogbesan, Oluwaseun; Donato, Anthony

2017-01-01

Necrotizing fasciitis is a fulminant soft tissue infection characterized by rapid progression and high mortality. Rituximab is a generally well-tolerated immunosuppresive medication used for B-cell malignancies and some rheumatological disorders. We report a case of a 69-year-old male with chronic lymphocytic leukemia who suffered necrotizing fasciitis of his left lower extremity secondary to Clostridium septicum 7 weeks after treatment with rituximab. Despite immediate intravenous antimicrobial therapy and emergent fasciotomy with extensive debridement, his hospital course was complicated by septic shock and he required an above-the-knee amputation. Physicians need to be aware of the possibility of necrotizing fasciitis in patients presenting with skin infections after rituximab therapy.

Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose rituximab is effective and tolerable and limits loss of CD20 expression by circulating CLL cells.

Science.gov (United States)

Zent, Clive S; Taylor, Ronald P; Lindorfer, Margaret A; Beum, Paul V; LaPlant, Betsy; Wu, Wenting; Call, Timothy G; Bowen, Deborah A; Conte, Michael J; Frederick, Lori A; Link, Brian K; Blackwell, Sue E; Veeramani, Suresh; Baig, Nisar A; Viswanatha, David S; Weiner, George J; Witzig, Thomas E

2014-07-01

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analog refractory disease or TP53 dysfunction still have limited treatment options and poor survival. Alemtuzumab-containing chemoimmunotherapy regimens can be effective but frequently cause serious infections. We report a Phase II trial testing the efficacy and tolerability of a short-duration regimen combining pentostatin, alemtuzumab, and low-dose high-frequency rituximab designed to decrease the risk of treatment-associated infections and to limit the loss of CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL that was either relapsed/refractory (n = 36) or previously untreated with 17p13 deletion (17p13-) (n = 3). Thirteen (33%) patients had both 17p13- and TP53 mutations predicted to be dysfunctional, and eight patients had purine analog refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed therapy, with only five (13%) patients having treatment-limiting toxicity and no treatment-related deaths. Twenty-two (56%) patients responded to treatment, with 11 (28%) complete responses (four with incomplete bone marrow recovery). Median progression-free survival was 7.2 months, time to next treatment was 9.1 months, and overall survival was 34.1 months. The majority of deaths (82%) were caused by progressive disease, including transformed diffuse large B-cell lymphoma (n = 6). Correlative studies showed that low-dose rituximab activates complement and natural killer cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that pentostatin, alemtuzumab, and low-dose high-frequency rituximab is a tolerable and effective therapy for CLL and that low-dose rituximab therapy can activate innate immune cytotoxic mechanisms without substantially decreasing CD20 expression. © 2014 Wiley Periodicals, Inc.

Impact of rituximab on patient-reported outcomes in patients with rheumatoid arthritis from the US Corrona Registry.

Science.gov (United States)

Harrold, Leslie R; John, Ani; Best, Jennie; Zlotnick, Steve; Karki, Chitra; Li, YouFu; Greenberg, Jeffrey D; Kremer, Joel M

2017-09-01

To evaluate the impact of rituximab on patient-reported outcomes (PROs) in a US-based observational cohort of patients with rheumatoid arthritis (RA). Patients with active RA, prior exposure to ≥1 tumor necrosis factor inhibitor (TNFi) and who newly initiated rituximab were identified. Changes in PROs were assessed 1 year after rituximab initiation. PRO measures included Clinical Disease Activity Index (CDAI); patient global disease activity, pain and fatigue (visual analog score; 0-100); morning stiffness (hours); modified Health Assessment Questionnaire (mHAQ; 0-3); and EuroQoL EQ-5D. Of the 667 patients who newly initiated rituximab, baseline PRO and clinical measures indicated that patients were substantially impacted by their RA disease and quality of life; 54% of patients had high disease activity. One year after rituximab initiation, 49.0, 47.1, 49.8, and 23.2% of patients reported clinically meaningful improvements in patient global, pain, fatigue, and mHAQ, respectively. Morning stiffness and EuroQol EQ-5D domains improved in 48 and 19-32% of patients, respectively. These real-world registry data demonstrated that patients with long-standing, refractory RA experienced improvements in PROs 1 year after initiating rituximab.

A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction.

Science.gov (United States)

Lafayette, Richard A; Canetta, Pietro A; Rovin, Brad H; Appel, Gerald B; Novak, Jan; Nath, Karl A; Sethi, Sanjeev; Tumlin, James A; Mehta, Kshama; Hogan, Marie; Erickson, Stephen; Julian, Bruce A; Leung, Nelson; Enders, Felicity T; Brown, Rhubell; Knoppova, Barbora; Hall, Stacy; Fervenza, Fernando C

2017-04-01

IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m 2 , to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8-2.4) mg/dl, and proteinuria was 2.1 (0.6-5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy. Copyright © 2017 by the American Society of Nephrology.

Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series

Directory of Open Access Journals (Sweden)

Mella Olav

2009-07-01

Full Text Available Abstract Background Chronic fatigue syndrome (CFS is a disease of unknown aetiology. A patient with CFS had unexpected, marked recovery of CFS symptoms lasting for five months during and after cytotoxic chemotherapy for Hodgkin's disease. We reasoned that the transient CFS recovery was related to methotrexate treatment, which induces immunomodulation in part through B-cell depletion. Methods In a case series, this patient and two additional CFS patients were B-cell depleted by infusion of the monoclonal anti-CD20 antibody rituximab. Results All three had improvement of all CFS symptoms. Patients 1 and 2 had major amelioration from 6 weeks after intervention, patient 3 slight improvement from the same time, but then improved markedly from 26 weeks after intervention. The symptomatic effect lasted until weeks 16, 18 and 44, respectively. At relapse, all were retreated with a single (patient 1 or double rituximab infusion (patients 2 and 3. Again, all three had marked symptom improvement, mimicking their first response. After new symptom recurrence, patients 1 and 2 were given weekly oral methotrexate, patient 1 having effect also from this agent. Patients 1 and 2 were again treated for a third rituximab infusion after new relapse, again with a marked clinical benefit. No unexpected toxicity was seen. Conclusion These observations suggest that B-lymphocytes are involved in CFS pathogenesis for a subset of patients. Benefit for all CFS symptoms, the delayed symptom relief following B-cell depletion, the kinetics of relapses, and the effect also from methotrexate treatment, provide suggestive evidence that B-cells play a significant role in the ongoing clinical features, and that CFS may be amenable to therapeutic interventions aimed at modifying B-cell number and function. More systematic investigations of this therapeutic strategy, and of its biological basis, are now needed.

Rituximab in the treatment of shrinking lung syndrome in systemic lupus erythematosus.

Science.gov (United States)

Peñacoba Toribio, Patricia; Córica Albani, María Emilia; Mayos Pérez, Mercedes; Rodríguez de la Serna, Arturo

2014-01-01

Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus. We report the case of a patient with non-responding SLS (neither to glucocorticoids nor immunosupresors), who showed remarkable improvement after the onset of treatment with rituximab. Although there is a little evidence, treatment with rituximab could be proposed in SLS when classical treatment fails. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Achieving a satisfactory clinical and biochemical response in antiphospholipid syndrome and severe thrombocytopenia with rituximab: two case reports.

Science.gov (United States)

Gamoudi, Donia; Cutajar, Melanie; Gamoudi, Nadia; Camilleri, David James; Gatt, Alex

2017-06-01

In AP syndrome (APS) with severe thrombocytopenia, rituximab represents a unique drug which can balance the effect of bleeding and thrombosis. By reducing the production of autoantibodies, rituximab can simultaneously raise the platelets and reduce the chance of thrombosis by suppressing APL antibodies. Rituximab can supersede splenectomy as second-line therapy in similar patients.

Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro.

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Khdair, Ayman; Handa, Hitesh; Mao, Guangzhao; Panyam, Jayanth

2009-02-01

Drug resistance limits the success of many anticancer drugs. Reduced accumulation of the drug at its intracellular site of action because of overexpression of efflux transporters such as P-glycoprotein (P-gp) is a major mechanism of drug resistance. In this study, we investigated whether photodynamic therapy (PDT) using methylene blue, also a P-gp inhibitor, can be used to enhance doxorubicin-induced cytotoxicity in drug-resistant tumor cells. Aerosol OT (AOT)-alginate nanoparticles were used as a carrier for the simultaneous cellular delivery of doxorubicin and methylene blue. Methylene blue was photoactivated using light of 665 nm wavelength. Induction of apoptosis and necrosis following treatment with combination chemotherapy and PDT was investigated in drug-resistant NCI/ADR-RES cells using flow cytometry and fluorescence microscopy. Effect of encapsulation in nanoparticles on the intracellular accumulation of doxorubicin and methylene blue was investigated qualitatively using fluorescence microscopy and was quantitated using HPLC. Encapsulation in AOT-alginate nanoparticles significantly enhanced the cytotoxicity of combination therapy in resistant tumor cells. Nanoparticle-mediated combination therapy resulted in a significant induction of both apoptosis and necrosis. Improvement in cytotoxicity could be correlated with enhanced intracellular and nuclear delivery of the two drugs. Further, nanoparticle-mediated combination therapy resulted in significantly elevated reactive oxygen species (ROS) production compared to single drug treatment. In conclusion, nanoparticle-mediated combination chemotherapy and PDT using doxorubicin and methylene blue was able to overcome resistance mechanisms and resulted in improved cytotoxicity in drug-resistant tumor cells.

Combination of chemotherapy, surgery and radiation in carcinoma ovary

International Nuclear Information System (INIS)

Dutta, T.K.; Mapa, M.K.; Gupta, B.D.; Dhall, G.I.

1979-01-01

The management of ovarian carcinoma is difficult mainly due to the fact that ovary, unlike other organs in the body remains the seat of wide variety of histological type of tumor with even wider biological behaviour and response to each modality of treatment. The objective of present paper is to evaluate the changing policy towards this tumor with emphasis on the combination plan in general and chemotherapy supplement in particular. Prognosis of advanced cancer which forms the bulk of the cases almost in every centre remains dismal. In this group of patients in a retrospective analysis, a guideline of treatment has been formulated. (auth.)

Preclinical safety, toxicology, and biodistribution study of adenoviral gene therapy with sVEGFR-2 and sVEGFR-3 combined with chemotherapy for ovarian cancer.

Science.gov (United States)

Tuppurainen, Laura; Sallinen, Hanna; Kokki, Emmi; Koponen, Jonna; Anttila, Maarit; Pulkkinen, Kati; Heikura, Tommi; Toivanen, Pyry; Hämäläinen, Kirsi; Kosma, Veli-Matti; Heinonen, Seppo; Alitalo, Kari; Ylä-Herttuala, Seppo

2013-03-01

Abstract Antiangiogenic and antilymphangiogenic gene therapy with soluble vascular endothelial growth factor receptor-2 (VEGFR-2) and soluble VEGFR-3 in combination with chemotherapy is a potential new treatment for ovarian carcinoma. We evaluated the safety, toxicology, and biodistribution of intravenous AdsVEGFR-2 and AdsVEGFR-3 combined with chemotherapy in healthy rats (n=90) before entering a clinical setting. The study groups were: AdLacZ and AdLacZ with chemotherapy as control groups, low dose AdsVEGFR-2 and AdsVEGFR-3, high dose AdsVEGFR-2 and AdsVEGFR-3, combination of low dose AdsVEGFR-2 and AdsVEGFR-3 with chemotherapy, combination of high dose AdsVEGFR-2 and AdVEGFR-3 with chemotherapy, and chemotherapy only. The follow-up time was 4 weeks. Safety and toxicology were assessed by monitoring the clinical status of the animals and by histological, hematological, and clinical chemistry parameters. For the biodistribution studies, quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used. Low dose (2×10(10) vp) AdsVEGFR-2 and AdsVEGFR-3 gene therapy was well tolerated, even when gene therapy was combined with chemotherapy. Notably, only transient elevation of liver enzymes and mild regenerative changes were seen in liver after the gene transfer in the groups that received high doses (2×10(11) vp) of AdsVEGFR-2 and AdsVEGFR-3 with or without chemotherapy. No life-threatening adverse effects were noticed in any of the treatment groups. The highest protein concentration of soluble VEGFR-2 (sVEGFR-2) in circulation was seen 1 week after the gene transfer. The combination of chemotherapy to gene therapy seemed to prolong the time of detectable transgene protein at least 1 week in the circulation. The expression of AdsVEGFR-2 and AdsVEGFR-3 transgenes was mainly seen in the liver and spleen as detected by qRT-PCR. According to these results, AdsVEGFR-2 and AdsVEGFR-3 gene therapy combined with

Assessment of serum tumor markers, tumor cell apoptosis and immune response in patients with advanced colon cancer after DC-CIK combined with intravenous chemotherapy

Directory of Open Access Journals (Sweden)

Lei-Fan Li

2016-12-01

Full Text Available Objective: To study the effect of DC-CIK combined with intravenous chemotherapy on serum tumor markers, tumor cell apoptosis and immune response in patients with advanced colon cancer. Methods: A total of 79 patients with advanced colon cancer conservatively treated in our hospital between May 2012 and October 2015 were retrospectively studied and divided into DC-CIK group and intravenous chemotherapy group according to different therapeutic regimens, DC-CIK group received DC-CIK combined with intravenous chemotherapy and intravenous chemotherapy group received conventional intravenous chemotherapy. After three cycles of chemotherapy, the content of tumor markers in serum, expression levels of apoptotic molecules in tumor lesions as well as immune function indexes were determined. Results: After 3 cycles of chemotherapy, CEA, CA199, CA242, HIF-1α, IL-4, IL-5 and IL-10 content in serum of DC-CIK group were significantly lower than those of intravenous chemotherapy group; p53, FAM96B, PTEN, PHLPP, ASPP2 and RASSF10 mRNA content in tumor lesions of DC-CIK group were significantly higher than those of intravenous chemotherapy group; the fluorescence intensity of CD3, CD4 and CD56 on peripheral blood mononuclear cell surface of DC-CIK group were significantly higher than those of intravenous chemotherapy group while the fluorescence intensity of CD8 and CD25 were significantly lower than those of intravenous chemotherapy group; IL-2 and IFN-γ content in serum of DC-CIK group were significantly higher than those of intravenous chemotherapy group while IL-4, IL-5 and IL-10 content were significantly lower than those of intravenous chemotherapy group. Conclusions: DC-CIK combined with intravenous chemotherapy has better effect on killing colon cancer cells and inducing colon cancer cell apoptosis than conventional intravenous chemotherapy, and can also improve the body's anti-tumor immune response.

Off-label use of rituximab in autoimmune disease in the Top End of the Northern Territory, 2008-2016.

Science.gov (United States)

Wongseelashote, Sarah; Tayal, Vipin; Bourke, Peter Francis

2018-02-01

Rituximab, an anti-CD20 B-cell depleting monoclonal antibody, is increasingly prescribed off-label for a range of autoimmune diseases. There has not previously been an audit of off-label rituximab use in the Northern Territory, where the majority of patients are Aboriginal. To evaluate retrospectively off-label rituximab use in autoimmune diseases in the Top End of the Northern Territory. We performed a retrospective audit of 8 years of off-label rituximab use at the Royal Darwin Hospital, the sole tertiary referral centre for the Darwin, Katherine and East Arnhem regions. Electronic and paper records were reviewed for demographic information, diagnosis/indication for rituximab, doses, previous/concomitant immunosuppression, clinical outcomes and specific adverse events. Rituximab was prescribed off-label to 66 patients for 24 autoimmune diseases. The majority of patients (62.1%) were Aboriginal and 60.6% female. The most common indications were refractory/relapsing disease despite standard therapies (68.7%) or severe disease with rituximab incorporated into an induction immunosuppressive regimen (19.4%). Systemic lupus erythematosus was the underlying diagnosis in 28.8% of cases. A clinically significant response was demonstrated in 74.2% of cases overall. There were 18 clinically significant infections; however, 13 were in patients receiving concurrent immunosuppressive therapy. There was a total of nine deaths from any cause. Rituximab has been used off-label for a range of autoimmune diseases in this population with a high proportion of Aboriginal patients successfully and safely in the majority of cases. © 2017 Royal Australasian College of Physicians.

Rituximab in the treatment of primary cutaneous B-cell lymphoma: a review.

Science.gov (United States)

Fernández-Guarino, M; Ortiz-Romero, P L; Fernández-Misa, R; Montalbán, C

2014-06-01

Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which is found in both normal and neoplastic B cells. In recent years, it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment (radiotherapy and surgery) of 2 types of indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma. Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma, leg type. Its use as an alternative drug led to it being administered intralesionally, with beneficial effects. In the present article, we review the literature published on the use of rituximab to treat primary cutaneous B-cell lymphoma. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

Experiencia con rituximab en miopatía inflamatoria idiopática refractaria

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Elmer R. García-Salazar

2013-10-01

Full Text Available Se describe las características clínicas y de laboratorio de dos pacientes que recibieron rituximab por miopatía inflamatoria idiopática (MII. Ellas eran refractarias a tratamiento convencional con DARMES, por lo que recibieron rituximab 1 gramo cada 14 días, en dos infusiones en ciclo semestral. En las historias clínicas se obtuvo los datos clínicos de fuerza muscular proximal, lesiones cutáneas patognomónicas, elevación de CPK, TGO, DHL y VSG, resultados de electromiografía, biopsia muscular y de piel. Ninguno de los dos casos presentó reacción medicamentosa ni infecciones durante y posterior a las infusiones. Rituximab mostró efectividad en la respuesta clínica y enzimática en estas pacientes con dermatomiositis refractarias a corticoides y DARMES tradicionales.

Internalisation of uncross-linked rituximab is not essential for the induction of caspase-independent killing in Burkitt lymphoma cell lines.

Science.gov (United States)

Turzanski, Julie; Daniels, Ian; Haynes, Andrew P

2008-08-01

Characterising the mechanisms underpinning caspase-independent programmed cell death (CI-PCD) induction by uncross-linked rituximab in B-cells may positively impact upon the treatment of disease states in which the classical apoptotic pathway is disabled. The necessity of rituximab internalisation for CI-PCD induction was investigated by flow cytometry and confocal microscopy in human BL cell lines with (e.g. Mutu I) and without (Mutu III) susceptibility to rituximab-induced killing. Flow cytometry demonstrated small, significant and similar amounts of rituximab internalisation by Mutu I cells after 1, 2, 4 and 24 h (p internalisation (p = 0.02, n = 5 and p = 0.0002, n = 6, respectively) in Mutu I cells, but confocal microscopy showed no correlation between internalised rituximab and phosphatidylserine exposure. We conclude that rituximab internalisation is not essential for CI-PCD induction in BL cell lines.

Outcome of 289 locally advanced non-small cell lung cancer treated with radiotherapy alone and radiotherapy combined with chemotherapy

International Nuclear Information System (INIS)

Ou Guangfei; Wang Lvhua; Zhang Hongxing; Chen Dongfu; Xiao Zefen; Feng Qinfu; Zhou Zongmei; Lv Jima; Liang Jun; Wang Mei; Yin Weibo

2007-01-01

Objective: To retrospectively analyze the outcome of locally advanced non-small cell lung cancer patients treated with radiotherapy and chemoradiotherapy. Methods: 289 patients who were treated either by radiotherapy alone (168 patients) or radiotherapy plus chemotherapy (121 patients) from Dec. 1999 to Dec. 2002 were entered into the database for analysis. Pathological types: squamous cancer (152), adenocarcinoma(74), squamoadenocarcinoma(2) and other types (2). 24 showed cancer unclassificable and 35 were diagnosed without pathological proof. Stages: 74 had III A and 215 III B stage disease. Among the 121 patients treated with combined modality, 24 were treated with concurrent chemoradiotherapy, 78 radiotherapy after chemotherapy(C + R), and 19 radiotherapy followed by chemotherapy(R + C). In patients treated by concurrent chemoradiotherapy or C + R, 38 received consolidation chemotherapy after induction treatment. Results: The 1-, 3-, 5-year overall survival, and the median survival were: 45% , 16% , 8%, and 16.2 months for all patients; 57%, 27%, 11%, and 21.7 months for stage IIIA; 41%, 12%, 7%, and 15.3 months for IIIB. By logrank test, clinical stage, KPS performance, tumor volume, hemoglobin level before treatment, consolidation chemotherapy, radiation dose, and response to treatment showed statistically dramatic impact on overall survival. The overall survival rate and median survival time were slightly higher in the combined group than in the radiotherapy alone group, but the difference is statistically insignificant. In Cox multivariable regression, stage and consolidation chemotherapy were independent prognostic factors; KPS performance, radiation dose, and response to treatment were at the margin of statistical significance. Esophagitis and pneumonitis of Grade II or higher were 24% and 8%, respectively. Failure sites included in the thorax(41%), outside of thorax(48%), and both in and outside the thorax(11%). There was no difference between the

Laser-assisted delivery of synergistic combination chemotherapy in in vivo skin.

Science.gov (United States)

Wenande, Emily; Tam, Joshua; Bhayana, Brijesh; Schlosser, Steven Kyle; Ishak, Emily; Farinelli, William A; Chlopik, Agata; Hoang, Mai P; Pinkhasov, Omar R; Caravan, Peter; Rox Anderson, R; Haedersdal, Merete

2018-04-10

The effectiveness of topical drugs for treatment of non-melanoma skin cancer is greatly reduced by insufficient penetration to deep skin layers. Ablative fractional lasers (AFLs) are known to enhance topical drug uptake by generating narrow microchannels through the skin, but information on AFL-drug delivery in in vivo conditions is limited. In this study, we examined pharmacokinetics, biodistribution and toxicity of two synergistic chemotherapy agents, cisplatin and 5-fluorouracil (5-FU), following AFL-assisted delivery alone or in combination in in vivo porcine skin. Detected at 0-120 h using mass spectrometry techniques, we demonstrated that fractional CO 2 laser pretreatment (196 microchannels/cm 2 , 852 μm ablation depth) leads to rapid drug uptake in 1500 μm deep skin layers, with a sixfold enhancement in peak cisplatin concentrations versus non-laser-treated controls (5 h, P = 0.005). Similarly, maximum 5-FU deposition was measured within an hour of AFL-delivery, and exceeded peak deposition in non-laser-exposed skin that had undergone topical drug exposure for 5 days. Overall, this accelerated and deeper cutaneous drug uptake resulted in significantly increased inflammatory and histopathological effects. Based on clinical scores and transepidermal water loss measurement, AFL intensified local toxic responses to drugs delivered alone and in combination, while systemic drug exposure remained undetectable. Quantitative histopathologic analyses correspondingly revealed significantly reduced epidermal proliferation and greater cellular apoptosis after AFL-drug delivery; particularly after combined cisplatin + 5-FU exposure. In sum, by overcoming the primary limitation of topical drug penetration and providing accelerated, enhanced and deeper delivery, AFL-assisted combination chemotherapy may represent a promising treatment strategy for non-melanoma skin cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

Bladder cancer: the combination of chemotherapy and irradiation in the treatment of patients with muscle-invading tumors

International Nuclear Information System (INIS)

Shipley, William U.; Zietman, Anthony L.

1995-01-01

In the USA the recommended treatment for patients with muscle-invading transitional cell cancer of the bladder is usually radical cystectomy. Conservative surgery (transurethral resection and partial cystectomy), irradiation, and cis-platinum based systemic chemotherapy are, however, each effective for some patients. Although they provide the opportunity for bladder preservation, each modality, when used alone, is inferior to radical cystectomy in terms of local control and, perhaps, survival. Initial response and local control rates are improved when a multimodality approach is used. Up to 85% of patients selected for bladder sparing therapy on the basis of their initial response to chemo-radiation may keep their bladders. This figure could increase further when other powerful prognostic factors, such as the presence of hydronephrosis or carcinoma in situ, are taken into account in initial patient selection. Deferring the patient from immediate cystectomy does not appear to compromise survival. The most appropriate sequencing of radiation and chemotherapy is yet to be established. Concomitant cis-platinum and irradiation improves local control and bladder preservation when compared with irradiation alone but does not decrease the metastatic rate. It is hoped that the well recognized activity of cis-platinum based combination chemotherapy in advanced disease will translate into effective eradication of micrometastatic disease (known to be present in up to 40% of patients at diagnosis). This has yet to be clearly demonstrated in a randomized trial. The addition of combination chemotherapy to radiation does not increase bladder morbidity but carries a considerable systemic risk. Thus, despite promising phase II studies, until a survival benefit is proven in a randomized trial, neoadjuvant or adjuvant combination chemotherapy in conjunction with irradiation should continue to be regarded as experimental

Successful pregnancy after rituximab in a women with recurrent in vitro fertilisation failures and anti-phospholipid antibody positive.

LENUS (Irish Health Repository)

Ng, C T

2012-02-01

We report a case of successful pregnancy after rituximab in a patient with a history of in vitro fertilisation (IVF) failures and positive anti-cardiolipin antibody (ACA). Following a course of rituximab, her ACA became negative and she successfully conceived with IVF treatment. This is the first case in literature describing the use of rituximab therapy in this clinical scenario.

Rituximab as a possible cause of posterior reversible encephalopathy syndrome

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Ahmed Imran Siddiqi

2011-09-01

Full Text Available A 66-year-old woman presented with new onset generalisedtonic-clonic seizures following her first dose ofchemotherapy comprising Rituximab, Cyclophosphamide,Hydroxydaunorubicin, Oncovin and Prednisolone (R-CHOP10 days earlier for non-Hodgkin’s lymphoma. On admission,computed tomography (CT scan of the cranium showed noabnormality. The CT was repeated within 48 hours as thepatient developed status epilepticus and papilledema; therepeat scan showed characteristics of posterior reversibleencephalopathy syndrome (PRES. Association of rituximabwith this condition was suspected as there was norecurrence of PRES after receiving two more cycles of CHOPwithout rituximab. Contrary to previously published casereports, this patient had a delayed clinical presentation.

Engaging the lysosomal compartment to combat B cell malignancies

DEFF Research Database (Denmark)

Gronbaek, K.; Jaattela, M.

2009-01-01

The combination of rituximab, a type I anti-CD20 mAb, with conventional chemotherapy has significantly improved the outcome of patients with B cell malignancies. Regardless of this success, many patients still relapse with therapy-resistant disease, highlighting the need for the development of m...

B cells and immunoglobulin in ABO-incompatible renal transplant patients receiving rituximab and double filtration plasmapheresis

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Meng-Kun Tsai

2015-04-01

Conclusion: With the aid of tacrolimus and mycophenolate mofetil, rituximab resulted in sustained suppression of B cell count and total IgG and IgM. Among the IgG subclasses, IgG3 was less sensitive to rituximab.

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial.

Science.gov (United States)

Jerkeman, Mats; Eskelund, Christian Winther; Hutchings, Martin; Räty, Riikka; Wader, Karin Fahl; Laurell, Anna; Toldbod, Helle; Pedersen, Lone Bredo; Niemann, Carsten Utoft; Dahl, Christina; Kuitunen, Hanne; Geisler, Christian H; Grønbæk, Kirsten; Kolstad, Arne

2018-03-01

Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data on either regimen alone. In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients aged 18 years or older with relapsed or refractory mantle cell lymphoma who had previously been treated with at least one rituximab-containing regimen, an Eastern Cooperative Oncology Group performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56 days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m 2 ) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle, whereas oral lenalidomide (15 mg once a day) was given on days 1-21. The primary endpoint was overall response assessed in the intention-to-treat population according to Lugano criteria. Safety analysis included all patients who received the treatment, irrespective of eligibility or duration of treatment. The trial is ongoing, but is no longer accruing patients, and is registered with ClinicalTrials.gov, number NCT02460276. Between April 30, 2015, and June 1, 2016, we enrolled 50 patients with relapsed or refractory mantle cell lymphoma at ten centres in Sweden, Finland, Norway, and Denmark. At a median follow-up of 17·8 months (IQR 14·7-20·9), 38 (76%, 95% CI 63-86) patients had an overall response, including 28 (56%, 42-69) patients who had a complete response and ten (20%, 11-33) who had a

Successful Treatment of a Bullous Pemphigoid Patient with Rituximab Who Was Refractory to Corticosteroid and Omalizumab Treatments

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Aslı Bilgiç Temel

2017-02-01

Full Text Available Omalizumab is a humanized monoclonal antibody which is an FDA-approved treatment of severe allergic asthma and inhibits IgE binding to FcεRI. According to increasing evidence of IgE inhibition, omalizumab was suggested as a therapeutic approach for bullous pemphigoid (BP. Rituximab has been reported to be effective in various autoimmune diseases, including autoimmune bullous dermatoses. A specific protocol for the use of rituximab to treat BP patients is not yet available. There are only small case series and case reports about the efficacy and safety of rituximab in BP. Here we present a young BP patient who responded well to rituximab therapy and was refractory to conventional and omalizumab therapies although he had elevated IgE levels and eosinophilia. Our case supports the knowledge about the effectiveness and safety of rituximab not only in pemphigus but also in BP. On the other hand, although it did not work in our case, omalizumab may be a potentially effective agent in some carefully selected patients with certain subtypes of BP.

A Case of Rituximab-Induced Necrotizing Fasciitis and a Review of the Literature

OpenAIRE

Abdulkareem, Abdullateef; D’Souza, Ryan S.; Shogbesan, Oluwaseun; Donato, Anthony

2017-01-01

Necrotizing fasciitis is a fulminant soft tissue infection characterized by rapid progression and high mortality. Rituximab is a generally well-tolerated immunosuppresive medication used for B-cell malignancies and some rheumatological disorders. We report a case of a 69-year-old male with chronic lymphocytic leukemia who suffered necrotizing fasciitis of his left lower extremity secondary to Clostridium septicum 7 weeks after treatment with rituximab. Despite immediate intravenous antimicrob...

The combination of radiotherapy and chemotherapy in the treatment of malignant tumours: indications and dangers

International Nuclear Information System (INIS)

Bartelink, H.; Somers, R.

1980-01-01

The combination of radiotherapy and chemotherapy has improved the results of treatment of certain malignant tumours. However, during both experimental investigations and clinical treatment, a number of severe side effects have been observed, during as well as some time after the administration, especially with use of actinomycin and adriamycin. Also the possibility exists that more secondary tumours are induced as the consequence of combination therapy. (Auth.)

{sup 99m}Tc-rituximab radiolabelled by photo-activation: a new non-Hodgkin's lymphoma imaging agent

Energy Technology Data Exchange (ETDEWEB)

Gmeiner Stopar, T.; Fettich, J.; Hojker, S. [University Medical Centre Ljubljana, Department for Nuclear Medicine, Ljubljana (Slovenia); Mlinaric-Rascan, I. [University of Ljubljana, Faculty of Pharmacy, Ljubljana (Slovenia); Mather, S.J. [St Bartholomew' s Hospital, Cancer Research UK, Department Nuclear Medicine, London (United Kingdom)

2006-01-01

Rituximab was the first chimeric monoclonal antibody to be approved for treatment of indolent B-cell non-Hodgkin's lymphoma (NHL). It is directed against the CD20 antigen, which is expressed by 95% of B-cell NHLs. The aim of this study was to explore the possibility of radiolabelling rituximab with {sup 99m}Tc for use as an imaging agent in NHL for early detection, staging, remission assessment, monitoring for metastatic spread and tumour recurrence, and assessment of CD20 expression prior to (radio)immunotherapy. Rituximab was purified from Mabthera solution (Roche), photo-activated at 302 nm by UV irradiation and radiolabelled with {sup 99m}Tc. The effectiveness of the labelling method was evaluated by determination of the number of free thiol groups per photoreduced antibody, radiochemical purity and in vitro stability of {sup 99m}Tc-rituximab. On average, 4.4 free thiol groups per photoreduced antibody were determined. Radiolabelling yields greater than 95% were routinely observed after storage of the photo-activated antibody at -80 C for 195 days. The direct binding assay showed preserved ability of {sup 99m}Tc-rituximab to bind to CD20, with an average immunoreactive fraction of 93.3%. The internalisation rate was proven to be low, with only 5.3% of bound {sup 99m}Tc-rituximab being internalised over 4 h at 37 C. Our results demonstrate that {sup 99m}Tc-rituximab of high radiochemical purity and with preserved binding affinity for the antigen can be prepared by photoreduction and that the method shows good reproducibility. {sup 99m}Tc-rituximab will be further explored as an imaging agent applicable in NHL for the purposes mentioned above. (orig.)

CHLORAMBUCIL PLUS RITUXIMAB AS FRONT-LINE THERAPY IN ELDERLY/UNFIT PATIENTS AFFECTED BY B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA: RESULTS OF A SINGLE-CENTRE EXPERIENCE.

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Luca Laurenti

2013-05-01

Full Text Available Currently standard first line therapy for fit patients with B-CLL/SLL are fludarabine-based regimens. Elderly patients or patients with comorbidities poorly tolerate purine analogue-based chemotherapy and they are often treated with Chlorambucil (Chl. However, complete response (CR and overall response (OR rates with Chl are relatively low. We now investigated whether the addition of Rituximab to Chl will improve the efficacy without impairing the tolerability in elderly and unfit patients. We included in our study 27 elderly or unfit patients that had not received prior therapy. All patients were treated with Chl (1mg/Kg per 28-day cycle for 8 cycles plus Rituximab (375 mg/m2 for the first course and 500 mg/m2 for subsequent cycles until the 6th cycle. We obtained an OR rate of 74%. The most frequent adverse effect was grade 3-4 neutropenia, which occurred in 18.5% of the patients. Infections or grade 3-4 extra-hematological side effects were not recorded. None of the patients required reduction of dose, delay of therapy or hospitalization. Overall, these data suggest that Chl-R is an effective and well tolerated regimen in elderly/unfit patients with CLL.

The long term effect and outcome of preoperative chemotherapy combined with radiation therapy for bladder cancer

International Nuclear Information System (INIS)

Nasu, Takahito; Nakane, Hiroshi; Kamata, Seiji; Mitsui, Hiroshi; Hayashida, Shigeaki; Shinohara, Youichi.

1996-01-01

The object of this study is to evaluate the efficacy of preoperative chemotherapy combined with radiation therapy for bladder cancer. A total of 44 patients with bladder cancer were treated by preoperative chemotherapy combined with radiation therapy between October, 1981 and December, 1986. Clinical stages included 4 patients in Ta, 25 in T1, 11 in T2, and 4 in T3. Each patient was treated twice with 15 gray of radiation to the small pelvic cavity and a chemotherapy combination of adriamycin, cis-platinum, tegaful, and peplomycin. The average observation time after the therapy was 83 month, with the maximum being 146 months. Complete remission was included in 5 patients, partial remission in 27, and no change in 12. Thus, the overall effective rate was 72.8%. Operations, selected by the results of the preoperative therapy, included transurethral resection on 28 patients, transurethral fulguration on 2, partial cystectomy on 4, resection of tumor on 4, and total cystectomy on 3. Operations were not performed on 2 patients and not allowed on 1 patient. The outcome during the long-term follow-up included cancer related deaths in 4 patients, and death resulting from other disorders in 9. The 5-year survival rates for superficial and invasive bladder cancer were 92.4%, and 83.9%, respectively. The 10-year survival rates for superficial and invasive bladder cancer were also 92.4% and 83.9%, respectively. The 3-year and 5-year non-recurrence rates for superficial bladder cancer were 75.8%, and 66.9% respectively, according to the Kaplan-Meier method. On the other hand, the 3-year and 5-year non-recurrence rates for invasive bladder cancer were both 73.8%. During the follow-up between 9 and 11 years, 3 upper tract tumor were diagnosed (2 ureteral cancer, and 1 renal pelvic cancer). We concluded that preoperative chemotherapy combined with radiation therapy may be effective for the treatment of bladder cancer. (author)

Rituximab as maintenance therapy for ANCA associated vasculitis: how, when and why?

Science.gov (United States)

Alba, Marco A; Flores-Suárez, Luis Felipe

2016-01-01

ANCA-associated vasculitides (AAV) are chronic autoimmune diseases characterized by inflammation and destruction of small vessels. Rituximab is now licensed for use as a remission-induction agent in the treatment of these disorders. During recent years, several non-controlled studies have suggested that rituximab may be of value in maintaining disease remission in AAV. In these series, 3 techniques have been tried: "watch-and-wait", repeated cycles in fixed intervals, or administration based on proposed biomarkers. More importantly, the results of the MAINRITSAN trial showed that this anti-CD20 agent is superior to azathioprine for preventing major relapses in AAV. This review summarizes current information regarding the effectiveness, timing, dosing, duration and safety of rituximab as a valid option for remission maintenance. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

In Vitro Cytotoxicity of Low-Dose-Rate Radioimmunotherapy by the Alpha-Emitting Radioimmunoconjugate Thorium-227-DOTA-Rituximab

International Nuclear Information System (INIS)

Dahle, Jostein; Krogh, Cecilie; Melhus, Katrine B.; Borrebaek, Jorgen; Larsen, Roy H.; Kvinnsland, Yngve

2009-01-01

Purpose: To determine whether the low-dose-rate α-particle-emitting radioimmunoconjugate 227 Th-1,4,7,10-p-isothiocyanato-benzyl-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (DOTA)-rituximab can be used to inactivate lymphoma cells growing as single cells and small colonies. Methods and Materials: CD20-positive lymphoma cell lines were treated with 227 Th-DOTA-rituximab for 1-5 weeks. To simulate the in vivo situation with continuous but decreasing supply of radioimmunoconjugates from the blood pool, the cells were not washed after incubation with 227 Th-DOTA-rituximab, but half of the medium was replaced with fresh medium, and cell concentration and cell-bound activity were determined every other day after start of incubation. A microdosimetric model was established to estimate the average number of hits in the nucleus for different localizations of activity. Results: There was a specific targeted effect on cell growth of the 227 Th-DOTA-rituximab treatment. Although the cells were not washed after incubation with 227 Th-DOTA-rituximab, the average contribution of activity in the medium to the mean dose was only 6%, whereas the average contribution from activity on the cells' own surface was 78%. The mean dose rates after incubation with 800 Bq/mL 227 Th-DOTA-rituximab varied from 0.01 to 0.03 cGy/min. The average delay in growing from 10 5 to 10 7 cells/mL was 15 days when the cells were treated with a mean absorbed radiation dose of 2 Gy α-particle radiation from 227 Th-DOTA-rituximab, whereas it was 11 days when the cells were irradiated with 6 Gy of X-radiation. The relative biologic effect of the treatment was estimated to be 2.9-3.4. Conclusions: The low-dose-rate radioimmunoconjugate 227 Th-DOTA-rituximab is suitable for inactivation of single lymphoma cells and small colonies of lymphoma cells.

Interferon-regulated chemokine score associated with improvement in disease activity in refractory myositis patients treated with rituximab.

Science.gov (United States)

López De Padilla, Consuelo M; Crowson, Cynthia S; Hein, Molly S; Strausbauch, Michael A; Aggarwal, Rohit; Levesque, Marc C; Ascherman, Dana P; Oddis, Chester V; Reed, Ann M

2015-01-01

The purpose of this study was to investigate whether serum interferon (IFN)-regulated chemokine and distinct cytokine response profiles are associated with clinical improvement in patients with refractory inflammatory myopathy treated with rituximab. In a randomised, placebo-phase trial Rituximab in Myositis Trial (RIM), 200 refractory adult and paediatric myositis subjects received rituximab. Following rituximab, clinical response and disease activity were assessed. Serum samples and clinical data were collected at baseline and several time-points after rituximab treatment. Multiplexed sandwich immunoassays quantified serum levels of IFN-regulated chemokines and other pro-inflammatory cytokines. Composite IFN-regulated chemokine and Th1, Th2, Th17 and regulatory cytokine scores were computed. Baseline IFN-regulated chemokine, Th1, Th2, Th17 and regulatory cytokine scores correlated with baseline physician global VAS, whereas the baseline Th1, Th2 and Th17 cytokine scores correlated with baseline muscle VAS. We also found baseline IFN-regulated chemokine scores correlated with specific non-muscular targets such as baseline cutaneous (r=0.29; p=0.002) and pulmonary (r=0.18; p=0.02) VAS scores. Among all cytokine/chemokines examined, the baseline score of IFN-regulated chemokines demonstrated the best correlation with changes in muscle VAS at 8 (r=-0.19; p=0.01) and 16 weeks (r=-0.17; p=0.03) following rituximab and physician global VAS at 16 weeks (r=-0.16; p=0.04). In vitro experiments showed increased levels of IL-8 (p=0.04), MCP-1 (p=0.04), IL-6 (p=0.03), IL-1β (p=0.04), IL-13 (p=0.04), IL-10 (p=0.02), IL-2 (p=0.04) and IFN-γ (p=0.02) in supernatants of TLR-3 stimulated PBMCs from non-responder compared to patients responders to rituximab. IFN-regulated chemokines before treatment is associated with improvement in disease activity measures in refractory myositis patients treated with rituximab.

Endometrial carcinoma in vitro chemosensitivity testing of single and combination chemotherapy regimens using the novel microculture kinetic apoptosis assay: implications for endometrial cancer treatment.

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Ballard, Karen S; Homesley, Howard D; Hodson, Charles; Presant, Cary A; Rutledge, James; Hallquist, Allan; Perree, Mathieu

2010-03-01

The in vitro microculture kinetic (MiCK) apoptosis assay has been used to predict single or combination chemotherapy response in leukemia patients. This feasibility study addressed MiCK in endometrial cancer specimens. Endometrial cancer specimens from total abdominal hysterectomies were processed at a central laboratory. Single cell suspensions of viable endometrial cancer cells were plated in individual wells. Single and combination regimens were tested: combinations of doxorubicin, cisplatin, and paclitaxel and carboplatin and paclitaxel (Gynecologic Oncology Group [GOG] 209 endometrial cancer phase III trial arms) as well as single agent testing with paclitaxel, carboplatin, doxorubicin, cisplatin, ifosfamide, and vincristine (active agents in GOG trials). Apoptosis was measured continuously over 48 hours. Fifteen of nineteen patients had successful assays. The highest mean chemo sensitivity was noted in the combination of cisplatin, doxorubicin, and paclitaxel with lower mean chemosensitivity for carboplatin and paclitaxel. Combination chemotherapy had higher chemosensitivity than single drug chemotherapy. However, in 25% of patients a single drug had higher chemosensitivity than combination chemotherapy. As single agents, ifosfamide, cisplatin, and paclitaxel had the highest kinetic unit values. Using a panel of agents simulating clinical dose regimens, the MiCK assay was feasible in evaluating in vitro chemosensitivity of endometrial cancer. MiCK assay results correlated with GOG clinical trial results. However, 25% of patients might be best treated with single agent chemotherapy selected by MiCK. Ifosfamide, cisplatin, and paclitaxel appear to have high activity as single agents. MiCK may be useful in future new drug testing and individualizing endometrial cancer patient's chemotherapy management.

The Results of Combined External Radiotherapy and Chemotherapy in the Management of Esophageal Cancer

International Nuclear Information System (INIS)

Lee, Hyun Joo; Suh, Hyun Suk; Kim, Jun Hee; Kim, Chul Soo; Kim, Sung Rok; Kim, Re Hwe

1996-01-01

Purpose : To evaluate the role of combination therapy of external radiotherapy and chemotherapy in the management of advanced esophageal cancer as a primary treatment compared with radiation therapy alone. Methods and Materials : A retrospective review of evaluable 55 esophageal cancer patients referred to the Department of Therapeutic Radiology, Paik Hospital for the external radiotherapy between Jul. 1983 and Dec.1994 was undertaken. Combined therapy patients (A group) were 30 and radiation alone patients (B group) were 25. Median age was 60 years old in A group(ranges : 42-81) and 65 years old in B group (ranges : 50-81). The male patients were 53. The fifty patients had squamous cell carcinomas. Radiation doses of 2520-6480c Gy were delivered over a period of 4-7 weeks. using 4MV LIVAC. Chemotherapy was administered in bolus injection before, after, or during the course of external radiotherapy. The local control rate and patterns of failure according to both treatment modalities and 1,2 year survival rates according to prognostic factors (stage, tumor length, radiation dose etc.) were analysed. Results : Median follow up period was 7 months (range : 2-73 months). Median survival was 7.5 months (20 days-29 months) in A group and 5 months(20 days-73 months) in B group. The 1,2 YSRs were 26.7%, 8.9% in A group. 12.7%, 4.3% in B group (p>0.05), respectively. The 1,2 YSRs according to stage(II/III), tumor length (5cm more or less). radiation dose(5000c Gy more or less) of A and B group were analyzed and the differences of survival rates of both treatments were not statistically significant. But among group B, patients who received 5000c Gy or more showed significant survival benefits (p<0.05). The treatment response rates of A and B group were 43.8%, 25.0%, respectively. Complete response rate of 25.0% in A and 8.3% in B were achieved. The local failure and distant metastasis were 52.4%, 23.8% in A group. 64.3%, 14.3% in B group, respectively. The combination

Novel use of rituximab in a case of Riedel's thyroiditis refractory to glucocorticoids and tamoxifen.

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Soh, Shui-Boon; Pham, Alan; O'Hehir, Robyn E; Cherk, Martin; Topliss, Duncan J

2013-09-01

A 42-year-old woman presented with a rapidly enlarging right-sided thyroid mass and underwent hemithyroidectomy. Riedel's thyroiditis was only diagnosed upon surgical decompression of the right carotid artery 2 years later. She became more symptomatic as Riedel's thyroiditis progressed, and mediastinal fibrosclerosis developed over the next 12 months. Oral prednisolone failed to improve her condition, and she was commenced on tamoxifen. Despite initial improvement, her symptoms recurred 2 years later, mainly arising from compression of the trachea and esophagus at the thoracic inlet. Fluorodeoxyglucose positron emission tomographic scan showed locally advanced active invasive fibrosclerosis in the neck and mediastinum. An elevated activin-A level of 218 pg/mL was consistent with active inflammation. IgG subtypes (including IgG4) were normal. Two courses of iv methylprednisolone were given but only produced transient improvement. Subsequently, the patient received 3 doses of i.v. rituximab at monthly intervals and had prompt sustained symptomatic improvement. Activin-A level decreased to 122 pg/mL 10 months after rituximab therapy. Fluorodeoxyglucose positron emission tomographic scan 6 weeks after therapy showed reduction in inflammation. A further scan at 10 months demonstrated ongoing response to rituximab. This is a case of refractory Riedel's thyroiditis with symptomatic, biochemical, and radiological improvement that has persisted 14 months after rituximab. The likelihood and duration of response to rituximab in Riedel's thyroiditis requires further study.

Defining the dose of gemtuzumab ozogamicin in combination with induction chemotherapy in acute myeloid leukemia

DEFF Research Database (Denmark)

Burnett, Alan; Cavenagh, Jamie; Russell, Nigel

2016-01-01

Arecent source data meta-analysis of randomized trials in adults assessing the immunoconjugate gemtuzumab ozogamicin combined with standard chemotherapy in acute myeloid leukemia showed a significant survival benefit in patients without an adverse karyotype. It is not clear whether the optimal dose...

Results of radiotherapy and a combined radio- and chemotherapy for hypopharyngeal carcinomas

International Nuclear Information System (INIS)

Mariya, Yasushi; Tarusawa, Nobuko; Takekawa, Shoichi; Yodono, Hiraku; Mori, Isao; Shinkawa, Hidekazu; Watanabe, Sadao; Miyano, Kazuo; Kattou, Keiichi.

1992-01-01

We analyzed the results of radiotherapy in 36 patients with hypopharyngeal carcinoma. The overall 2-year and 5-year survival rates were 45.3% and 31.1%, respectively. For 23 patients given radical irradiation, the corresponding figures were 37.8% and 28.3%. However, in 16 patients receiving a combined therapy of radical irradiation and chemotherapy, mainly an intraarterial injection of cisplatin, the survivals were better; the 2-year survival rate was 50.0% and four patients have survived for more than three years without recurrence. In managing patients with hypopharyngeal carcinoma, this combined therapy would improve therapeutic outcome and also assist in larynx preservation. (J.P.N.)

Remission Time after Rituximab Treatment for Autoimmune Bullous Disease: A Proposed Update Definition.

Science.gov (United States)

Iranzo, Pilar; Pigem, Ramon; Giavedoni, Priscila; Alsina-Gibert, Mercè

2015-01-01

A therapeutic endpoint is a very important tool to evaluate response in clinical trials. In 2005, a consensus statement identified two late endpoints of disease activity in pemphigus: complete remission off therapy and complete remission on therapy, both definitions applying to patients without lesions for at least 2 months. The same period of time was considered for partial remission off/on therapy. These definitions were later applied to bullous pemphigoid and are considered in most studies on autoimmune bullous disease. These endpoints were established for different adjuvant agents, but at that moment, rituximab was not considered. Rituximab is known for the long duration of its effect, and in most studies relapses have been reported later than 6 months after treatment. In our opinion, time to remission after rituximab treatment should be redefined. © 2015 S. Karger AG, Basel.

Chemotherapy or radio-chemotherapy for advanced adenocarcinoma of the oesophagus and cardiac orifice

International Nuclear Information System (INIS)

Seitz, J.F.; Duffaud, F.; Dahan, L.; Ries, P.; Ville, E.; Laugier, R.

2001-01-01

Adenocarcinomas of esophagus and cardia represent in France approximately 20 to 40% of the esophagus cancers. They have a high risk to develop lymph nodes metastases and liver metastases. Currently, only 50 to 70% of patients may benefit from surgical curative resection at diagnosis, but more than 50% of them will recur. The standard of treatment of these metastatic adenocarcinomas is chemotherapy. Three large randomized comparative studies, between chemotherapy and supportive care, showed that chemotherapy significantly extends the median of survival (from 3-4 months to 10-12 months) and improves the quality of life. Currently, the combination of epirubicin-cisplatin-continuous 5FU (ECF) is the most effective regimen but it is difficult to administer and tolerate because of the long continuous 5FU infusion. In France, the most commonly used combination regimen still associates 5FU and cisplatin. New drugs (such as docetaxel, CPT11, oxaliplatin) used alone or in combination, especially with 5U, are very promising. Radio-chemotherapy is the preferred treatment for locoregional recurrences, because it improves dysphagia and enables to obtain complete tumor responses. Current results from concomitant radio-chemotherapy studies for esophagus cancer, based on 5FU alone, 5FU-cisplatin or 5FU-mitomycin, given as preoperative treatment or as exclusive treatment, support to use radio-chemotherapy for the treatment of loco-regional recurrences after surgical resection. Nevertheless, the optimal radio-chemotherapy schedule still remain to be defined (dose, duration, splitting of radiotherapy, choice of anticancer drugs). (authors)

Identification of relevant drugable targets in diffuse large B-cell lymphoma using a genome-wide unbiased CD20 guilt-by association approach

NARCIS (Netherlands)

de Jong, Mathilde R. W.; Visser, Lydia; Huls, Gerwin; Diepstra, Arjan; van Vugt, Marcel; Ammatuna, Emanuele; van Rijn, Rozemarijn S.; Vellenga, Edo; van den Berg, Anke; Fehrmann, Rudolf S. N.; van Meerten, Tom

2018-01-01

Forty percent of patients with diffuse large B-cell lymphoma (DLBCL) show resistant disease to standard chemotherapy (CHOP) in combination with the anti-CD20 monoclonal antibody rituximab (R). Although many new anti-cancer drugs were developed in the last years, it is unclear which of these drugs

Malignant strictures involving the esophagogastric junction : palliative treatment with balloon dilation combined with chemotherapy and/or radiotherapy

International Nuclear Information System (INIS)

Hong, Hyoek Jin; Ko, Gi Young; Song, Ho Young; Cho, Yong Soo; Sung, Kyu Bo

2001-01-01

To overcome the limitations of expandable metallic stent placement by using balloon dilation combined with chemotherapy or radiation therapy in the treatment of malignant esophageal strictures involving the esophagogastric junction (EGJ). Fluoroscopically guided balloon dilation was performed in 14 patients with strictures due to squamous cell carcinoma (n=5) or adenocarcinoma (n=9). After balloon dilation all patients underwent chemotherapy or radiation therapy. There were no failures or major complications After dilation, dysphagia improved in 13 (92%) of 14 patients, and the long-term success rate was 50%. Six of the seven patients in whom the condition recurred underwent further balloon dilation (n=4) or placement of an expandable metallic stent (n=2). Ten of the 13 who were followed up died after diffuse metastasis. Prior to their eventual death (mean survial, 20 weeks), the dysphagia experienced by seven (70%) of these ten improved, and thus they required no further treatment. Balloon dilation combined with chemotherapy or radiation therapy seems to be a safe and effective secondary therapy for patients with dysphagia due to malignant stricture involving the EGJ

Absolute lymphocyte count predicts response to rituximab-containing salvage treatment for relapsed/refractory B-cell non-Hodgkin's lymphoma with prior rituximab exposure

Directory of Open Access Journals (Sweden)

Man-Hsin Hung

2013-04-01

Conclusion: Our study results show that for patients with relapsed/refractory B-cell NHL, rituximab-containing salvage treatment is feasible and generally tolerable. A high ALC-R value was significantly associated with a better response to this treatment.

Combined photothermo-chemotherapy using gold nanoshells on drug-loaded micelles for colorectal cancer treatment

Science.gov (United States)

Lee, Shin-Yu; Shieh, Ming-Jium

2018-02-01

Combined photothermo-chemotherapy is a new strategy for cancer treatment which improves the therapeutic outcome by synergistic effects of both therapies. Here, we presented a multifunctional gold nanoshell that exhibited excellent photothermal conversion and delivered the hydrophobic chemotherapy drug, SN-38. The positively charged SN-38-loaded PDMA-PCL micelles were decorated with a gold layer by in situ reduction of chloroauric acid on the surface of micelles. Scanning and transmission electron microscopy images proved micelles were successfully decorated and the resulting gold nanoshells had a spherical morphology with a narrow size distribution. The synthesized gold nanoshells displayed a broad surface plasmon resonance peak in the near-infrared wavelength region and a great photothermal conversion ability. After pegylation, gold nanoshells were stable in biological media and appeared highly biocompatible in the absence of laser irradiation. Upon near-infrared laser irradiation, incident energy was converted into heat by gold nanoshells on SN-38-loaded micelles (SN-38@pGNS), which causes local temperature increase and triggers the release of encapsulated drug. Compared to SN-38, SN-38-loaded micelles, or laser with drug-free gold nanoshells alone, combined photothermo-chemotherapy using SN-38@pGNS with laser irradiation killed colorectal cancer cells with higher efficacy in vitro and demonstrated significant tumor suppression in vivo, suggesting that gold nanoshells on drug-loaded micelles delivered SN-38 and photothermal therapy in synergistic actions and might be a potential candidate for future colorectal cancer therapy.

Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab

Directory of Open Access Journals (Sweden)

Theodore-Oklota C

2016-09-01

Full Text Available Christina Theodore-Oklota,1 Louise Humphrey,2 Christof Wiesner,1 Gabriel Schnetzler,3 Stacie Hudgens,4 Alicyn Campbell1 1Genentech, South San Francisco, CA, USA; 2Adelphi Values, Macclesfield, Cheshire, UK; 3F. Hoffmann La-Roche Ltd, Basel, Switzerland; 4Clinical Outcomes Solutions, Tucson, AZ, USA Background: A subcutaneous (SC formulation of rituximab (MabThera®/Rituxan® has been developed that could reduce administration time and improve patient satisfaction with treatment. The Rituximab Administration Satisfaction Questionnaire (RASQ was created to assess patients’ perceptions and satisfaction with rituximab SC (RASQ-SC or rituximab intravenous (RASQ-IV. We assessed the content validity and psychometric properties of RASQ in patients with non-Hodgkin lymphoma.Methods: Face and content validity of RASQ-SC and RASQ-IV were qualitatively assessed using 60-minute combined concept elicitation and cognitive debriefing interviews. Psychometric validation of RASQ (item performance and reliability was assessed quantitatively against the established Cancer Therapy Satisfaction Questionnaire (CTSQ, using questionnaire data from the PrefMab (NCT01724021 and MabCute (NCT01461928 clinical studies.Results: RASQ-IV demonstrated excellent coverage of concepts relevant to patients’ (n=10 own treatment experiences and no new concepts were identified. Patients’ expectations of rituximab SC were conceptually consistent with items included in the RASQ-SC, suggesting that the tool is also conceptually adequate. In 1,051 patients from PrefMab and MabCute, correlations with domains such as “RASQ: Physical Impacts” and “CTSQ: Feelings About Side Effects”, “RASQ: Physical Impacts” and “CTSQ: Satisfaction With Therapy”, and “RASQ: Satisfaction” and “CTSQ: Satisfaction With Therapy”, achieved moderate-to-high correlations (>0.4 for convergent domains and <0.3 for divergent domains.Conclusion: This study supports the qualitative face and

Effect of preoperative oral S-1 combined with regional intra-arterial chemotherapy on malignant molecule expression in locally advanced unresectable gastric cancer tissue

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Lei Liu

2016-11-01

Full Text Available Objective: To study the effect of preoperative oral S-1 combined with regional intra-arterial chemotherapy on malignant molecule expression in locally advanced unresectable gastric cancer tissue. Methods: A total of 144 patients with locally advanced gastric cancer receiving surgical resection after neoadjuvant chemotherapy in our hospital between May 2012 and August 2015 were selected and randomly divided into experimental group who received preoperative oral S-1 combined with regional intra-arterial chemotherapy and control group who received preoperative intravenous systemic chemotherapy. The levels of serum tumor markers were determined after chemotherapy, and the expression levels of tumor suppressor genes and cell cycle-related molecules in tumor tissue were determined after surgical resection. Results: After neoadjuvant chemotherapy, the serum G-17, TK-1, CEA, CA19-9, CA12-5, CA72-4 and CK, CK-MB, ALT, AST levels of experimental group were significantly lower than those of control group; after surgical resection, the p16, p27, PTEN and TXNIP mRNA levels in tumor tissue of experimental group were significantly higher than those of control group while CyclinB2, CyclinD1, CyclinE, CDK1 and CDK2 mRNA levels were significantly lower than those of control group. Conclusions: Preoperative oral S-1 combined with regional intra-arterial chemotherapy can more effectively kill gastric cancer cells, reduce tumor load, inhibit cell cycle and promote cell apoptosis.

Ovarian carcinoma: Role of radiation therapy versus chemotherapy

International Nuclear Information System (INIS)

Shehata, W.M.; Meyer, R.L.; Cormier, W.J.; Jazy, F.K.

1986-01-01

The authors evaluated 83 patients with ovarian cancer who were irradiated or treated by a combination of cytoxan, adriamycin, and cisplatin. According to FIGO stage, eight patients had stage I disease, 12 had stage II disease, 61 had stage II disease and two has stage IV disease. Fifty patients had bulky disease and 33 had minimal disease of 2 cm or less. Sixty patients were irradiated to an open abdominopelvic field (30 Gy delivered over 4 weeks), with or without a pelvic boost. Fifty-five patients received combination chemotherapy and 30 received a single agent as initial therapy. The patients were divided into three groups. The 26 patients in group I received primary radiation therapy with or with out adjuvant single-agent chemotherapy, then combination chemotherapy to salvage. The 34 patients in group II were irradiated after chemotherapy, mainly combination chemotherapy, failed. The 23 patients in group III received, mainly combination chemotherapy with second-line drugs for salvage

Bevacizumab-Based Chemotherapy Combined with Regional Deep Capacitive Hyperthermia in Metastatic Cancer Patients: A Pilot Study.

Science.gov (United States)

Ranieri, Girolamo; Ferrari, Cristina; Di Palo, Alessandra; Marech, Ilaria; Porcelli, Mariangela; Falagario, Gianmarco; Ritrovato, Fabiana; Ramunni, Luigi; Fanelli, Margherita; Rubini, Giuseppe; Gadaleta, Cosmo Damiano

2017-07-06

As an angiogenesis inhibitor, bevacizumab has been investigated in combination with different chemotherapeutic agents, achieving an established role for metastatic cancer treatment. However, potential synergic anti-angiogenic effects of hyperthermia have not tested to date in literature. The aim of our study was to analyze efficacy, safety, and survival of anti-angiogenic-based chemotherapy associated to regional deep capacitive hyperthermia (HT) in metastatic cancer patients. Twenty-three patients with metastatic colorectal ( n = 16), ovarian ( n = 5), and breast ( n = 2) cancer were treated with HT in addition to a standard bevacizumab-based chemotherapy regimen. Treatment response assessment was performed, according to the modified Response Evaluation Criteria for Solid Tumors (mRECIST), at 80 days (timepoint-1) and at 160 days (timepoint-2) after therapy. Disease Response Rate (DRR), considered as the proportion of patients who had the best response rating (complete response (CR), partial response (PR), or stable disease (SD)), was assessed at timepoint-1 and timepoint-2. Chi-squared for linear trend test was performed to evaluated the association between response groups (R/NR) and the number of previous treatment (none, 1, 2, 3), number of chemotherapy cycles (12), number of hyperthermia sessions (24), and lines of chemotherapy (I, II). Survival curves were estimated by Kaplan-Meier method. DRR was 85.7% and 72.2% at timepoint-1 and timepoint-2, respectively. HT was well tolerated without additional adverse effects on chemotherapy-related toxicity. Chi-squared for linear trend test demonstrated that the percentage of responders grew in relation to the number of chemotherapy cycles ( p = 0.015) and to number of HT sessions ( p chemotherapy cycles ( p chemotherapy with HT has a favorable tumor response, is feasible and well tolerated, and offers a potentially promising option for metastatic cancer patients.

Efficacy and Safety of rh-Endostatin Combined with Chemotherapy 
versus Chemotherapy Alone for Advanced NSCLC: A Meta-analysis Review

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Jinzhong ZHANG

2011-05-01

Full Text Available Background and objective In recent years, there has been a large number of studies and reports about the efficacy and safety of recombinant human endostatin (rh-endostatin, an anti-angiogenic drug, in treatment of advanced lung cancer. Authentic assessment of rh-endostatin treatment in lung cancer is important. The aim of this study is to assess the clinical efficacy and safety of rh-endostatin combined with chemotherapy in the treatment of patients with non-small cell lung cancer (NSCLC. Methods Cochrane systematic review methods were used in the data selection, and data were selected from the Cochrane Library, EMBASE, Medline, SCI, CBM, CNKI, and etc electronic database to get all clinical controlled trials. The retrieval time was March 2010. The objects of these randomized controlled trials were advanced NSCLC patients and in the experimental group was rh-endostatin combination chemotherapy, in the control group was chemotherapy alone to compare the efficacy of two groups. The quality of included trials were evaluated by two reviewers independently. The software RevMan 5.0 was used for meta-analyses. Results Fifteen trials with 1,326 patients were included according to the including criterion. All trials were randomized controlled trials, and two trials were adequate in reporting randomization. Thirteen trials didn’t mention the blinding methods. Meta analysis indicated that the NPE arm (Vinorelbine+cisplatin+rh-endostatin had a different response rate compared with NP (Vinorelbine+cisplatin arm (OR=2.16, 95%CI: 1.57-2.99. The incidences of severe leukopenia (OR=0.94, 95%CI: 0.66-1.32 and severe thrombocytopenia (OR=1.00, 95%CI: 0.64-1.57 and nausea and vomiting (OR=0.85, 95%CI: 0.61-1.20 were similar in the NPE arm compared with those in the NP arm. The NPE plus radiotherapy (RT arm had a similar response rate compared with NP plus RT arm (OR=2.39, 95%CI: 0.99-5.79. The incidences of leukopenia (OR=0.83, 95%CI: 0.35-1.94 and

Gemcitabine-Based Combination Chemotherapy Followed by Radiation With Capecitabine as Adjuvant Therapy for Resected Pancreas Cancer

International Nuclear Information System (INIS)

Desai, Sameer; Ben-Josef, Edgar; Griffith, Kent A.; Simeone, Diane; Greenson, Joel K.; Francis, Isaac R.; Hampton, Janet; Colletti, Lisa; Chang, Alfred E.; Lawrence, Theodore S.; Zalupski, Mark M.

2009-01-01

Purpose: To report outcomes for patients with resected pancreas cancer treated with an adjuvant regimen consisting of gemcitabine-based combination chemotherapy followed by capecitabine and radiation. Patients and Methods: We performed a retrospective review of a series of patients treated at a single institution with a common postoperative adjuvant program. Between January 2002 and August 2006, 43 resected pancreas cancer patients were offered treatment consisting of 4, 21-day cycles of gemcitabine 1 g/m 2 intravenously over 30 min on Days 1 and 8, with either cisplatin 35 mg/m 2 intravenously on Days 1 and 8 or capecitabine 1500 mg/m 2 orally in divided doses on Days 1-14. After completion of combination chemotherapy, patients received a course of radiotherapy (54 Gy) with concurrent capecitabine (1330 mg/m 2 orally in divided doses) day 1 to treatment completion. Results: Forty-one patients were treated. Median progression-free survival for the entire group was 21.7 months (95% confidence interval 13.9-34.5 months), and median overall survival was 45.9 months. In multivariate analysis a postoperative CA 19-9 level of ≥180 U/mL predicted relapse and death. Toxicity was mild, with only two hospitalizations during adjuvant therapy. Conclusions: A postoperative adjuvant program using combination chemotherapy with gemcitabine and either cisplatin or capecitabine followed by radiotherapy with capecitabine is tolerable and efficacious and should be considered for Phase III testing in this group of patients.

Hemangiosarcoma in a Dog: Unusual Presentation and Increased Survival Using a Complementary/Holistic Approach Combined with Metronomic Chemotherapy

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Philip Chaikin

2018-01-01

Full Text Available This case report documents the clinical and pathologic findings in a 12-year-old terrier mix with intraocular and splenic hemangiosarcoma. Pathologic findings in both the spleen and globe were consistent with hemangiosarcoma with a low mitotic count. Initial treatment consisted of enucleation and then splenectomy followed by one cycle of conventional doxorubicin chemotherapy. Due to poor tolerance, a subsequent treatment regimen consisted of metronomic chemotherapy with chlorambucil combined with an alternative/complementary regimen of I’m-Yunity (polysaccharopeptide and Yunnan Baiyao. Follow-up thoracic radiographs and abdominal ultrasounds over a period of 24 months showed no evidence of pulmonary, hepatic, or right atrial metastases, during which time the patient had an excellent quality of life. However, shortly after achieving two-year survival, the patient developed new onset seizures unresponsive to anticonvulsant therapy. Therefore, a decision was made to euthanize the dog given that the most likely etiology of the seizures was a brain tumor. Overall, this is an exceptional treatment response given the poor survival statistics of hemangiosarcoma even with conventional chemotherapy. However, additional clinical pharmacology and clinical trial data are needed to further support the use of a complementary/holistic approach in combination with metronomic chemotherapy.

Potent antitumor activities of recombinant human PDCD5 protein in combination with chemotherapy drugs in K562 cells

International Nuclear Information System (INIS)

Shi, Lin; Song, Quansheng; Zhang, Yingmei; Lou, Yaxin; Wang, Yanfang; Tian, Linjie; Zheng, Yi; Ma, Dalong; Ke, Xiaoyan; Wang, Ying

2010-01-01

Conventional chemotherapy is still frequently used. Programmed cell death 5 (PDCD5) enhances apoptosis of various tumor cells triggered by certain stimuli and is lowly expressed in leukemic cells from chronic myelogenous leukemia patients. Here, we describe for the first time that recombinant human PDCD5 protein (rhPDCD5) in combination with chemotherapy drugs has potent antitumor effects on chronic myelogenous leukemia K562 cells in vitro and in vivo. The antitumor efficacy of rhPDCD5 protein with chemotherapy drugs, idarubicin (IDR) or cytarabine (Ara-C), was examined in K562 cells in vitro and K562 xenograft tumor models in vivo. rhPDCD5 protein markedly increased the apoptosis rates and decreased the colony-forming capability of K562 cells after the combined treatment with IDR or Ara-C. rhPDCD5 protein by intraperitoneal administration dramatically improved the antitumor effects of IDR treatment in the K562 xenograft model. The tumor sizes and cell proliferation were significantly decreased; and TUNEL positive cells were significantly increased in the combined group with rhPDCD5 protein and IDR treatment compared with single IDR treatment groups. rhPDCD5 protein, in combination with IDR, has potent antitumor effects on chronic myelogenous leukemia K562 cells and may be a novel and promising agent for the treatment of chronic myelogenous leukemia.

Advanced epithelial ovarian cancer: toxicity of whole abdominal irradiation after operation, combination chemotherapy, and reoperation

International Nuclear Information System (INIS)

Schray, M.F.; Martinez, A.; Howes, A.E.; Ballon, S.C.; Podratz, K.C.; Sikic, B.I.; Malkasian, G.D.

1986-01-01

Thirty-five patients with advanced ovarian cancer have received, as salvage therapy, irradiation consisting of 30 Gy to the entire abdominal contents with partial liver/kidney shielding and boosts to 42 and 51 Gy for the paraaortic/diaphragmatic and pelvic regions, respectively. These patients had received 6 to 25 cycles (median, 11 cycles) of prior combination chemotherapy (included cisplatin in 30), with second-look laparotomy performed in 33; 24 (68%) had three or more laparotomies. Acute gastrointestinal toxicity was generally mild. Significant hematologic toxicity (leukocytes less than 2000/mm3; or platelets less than 100,000/mm3) was seen in 19 (54%); platelet suppression occurred in 18 of these 19. Nine patients failed to complete the prescribed course of therapy; in seven, this was secondary to hematologic toxicity. Amount of prior chemotherapy and advanced age correlated with degree of hematologic toxicity. Five patients without evidence of disease (laparotomy confirmed) have developed treatment-related bowel obstruction. No other chronic toxicity of clinical significance has been observed. Seven patients have developed bowel obstruction associated with progressive neoplasm. Irradiation was well tolerated symptomatically, but hematologic toxicity associated with prior chemotherapy prevented its completion in 20% of patients. Clinical manifestations of radiation bowel toxicity have been moderate to date and should be interpreted in the context of the aggressive combined modality program

Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis

NARCIS (Netherlands)

Isaacs, John D.; Cohen, Stanley B.; Emery, Paul; Tak, Paul P.; Wang, Jianmei; Lei, Guiyuan; Williams, Sarah; Lal, Preeti; Read, Simon J.

2013-01-01

Studies examining the relationship between serological status (rheumatoid factor and/or anticitrullinated antibody) and rituximab treatment outcome in rheumatoid arthritis (RA) have been hampered by limited numbers of seronegative patients. To carry out a meta-analysis of trials from the rituximab

Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas.

Science.gov (United States)

Cortelazzo, Sergio; Tarella, Corrado; Gianni, Alessandro Massimo; Ladetto, Marco; Barbui, Anna Maria; Rossi, Andrea; Gritti, Giuseppe; Corradini, Paolo; Di Nicola, Massimo; Patti, Caterina; Mulé, Antonino; Zanni, Manuela; Zoli, Valerio; Billio, Atto; Piccin, Andrea; Negri, Giovanni; Castellino, Claudia; Di Raimondo, Francesco; Ferreri, Andrés J M; Benedetti, Fabio; La Nasa, Giorgio; Gini, Guido; Trentin, Livio; Frezzato, Maurizio; Flenghi, Leonardo; Falorio, Simona; Chilosi, Marco; Bruna, Riccardo; Tabanelli, Valentina; Pileri, Stefano; Masciulli, Arianna; Delaini, Federica; Boschini, Cristina; Rambaldi, Alessandro

2016-11-20

Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis. Results Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% ( P = .83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = .12), or overall survival (74% v 77%, respectively; P = .64). Significantly higher hematologic toxicity ( P < .001) and more infectious complications ( P < .001) were observed in the R-HDS arm. Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.

Small-cell carcinoma of the esophagus with regression after combination chemotherapy and radiation therapy

International Nuclear Information System (INIS)

Hirsch, J.A.; Levine, M.S.; Silberg, D.G.; Phillipe, L.

1995-01-01

The authors present an unusual case of small-cell carcinoma of the esophagus, which manifested on double-contrast esophagography as an ulcerated submucosal mass. The lesion underwent dramatic regression after combination chemotherapy and radiation therapy, which has occasionally been used as an alternative to surgery in patients with this rare but aggressive esophageal neoplasm. (author). 8 refs., 4 figs

Development and biological studies of ¹⁷⁷Lu-DOTA-rituximab for the treatment of Non-Hodgkin's lymphoma.

Science.gov (United States)

Massicano, Adriana V F; Pujatti, Priscilla B; Alcarde, Lais F; Suzuki, Miriam F; Spencer, Patrick J; Araújo, Elaine B

2016-01-01

The optimization of DOTA-NHS-ester conjugation to Rituximab using different Ab:DOTA molar ratios (1:10, 1:20, 1:50 and 1:100) was studied. High radiochemical yield, in vitro stability and immunoreactive fraction were obtained for the Rituximab conjugated at 1:50 molar ratio, resulting in the incorporation of an average number of 4.9 ± 1.1 DOTA per Rituximab molecule. Labeling with 177Lu was performed in high specific activity with great in vitro stability. Biodistribution in healthy and xenographed mice showed tumor uptake and high in vivo stability as evidenced by low uptake in bone. The properties of 177Lu-DOTA-Rituximab prepared from DOTA-NHS-ester suggest the potential for the application of the 177Lu-labeled antibody in preliminary clinical studies.

Combined treatment with immunoadsorption and rituximab leads to fast and prolonged clinical remission in difficult-to-treat pemphigus vulgaris.

Science.gov (United States)

Behzad, M; Möbs, C; Kneisel, A; Möller, M; Hoyer, J; Hertl, M; Eming, R

2012-04-01

Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune bullous disorder which is characterized by blisters and erosions of the skin and mucous membranes. A frequently applied first-line therapy for PV consists of systemic corticosteroids (CS) combined with immunosuppressive agents. In refractory cases, novel therapeutic strategies such as immunoadsorption (IA) and the anti-CD20 antibody rituximab (Rtx) aim at directly interfering with pathogenic autoantibodies (auto-Abs). To investigate the long-term efficacy of IA in combination with Rtx in patients with difficult-to-treat PV, we assessed the clinical response to treatment by monitoring the Autoimmune Bullous Skin Disorder Intensity Score, IgG auto-Abs against desmoglein 1 and 3 (Dsg1 and Dsg3) and the dose of systemic CS. We retrospectively analysed clinical and serological parameters of 10 patients with difficult-to-treat PV who received IA at 4-week intervals, followed by Rtx either twice at 1000 mg or four times at 375mg m(-2) . During a 12-month follow-up period, CS were tapered according to the individual clinical status. Six months after the first IA treatment eight of 10 patients were in complete remission on therapy while one patient showed a partial response and one patient was unresponsive to the treatment. At 12 months, six of eight patients were in complete remission on therapy, one patient showed stable disease and one patient had relapsed. Overall, anti-Dsg3 IgG and anti-Dsg1 IgG auto-Abs correlated well with the clinical activity and systemic CS were tapered gradually. The present findings show that the combination of IA and Rtx induces rapid clinical remission and long-term control in difficult-to-treat pemphigus. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Histopathological studies of radiation-combined intra-arterial chemotherapy on squamous cell carcinoma of the mandible

International Nuclear Information System (INIS)

Yonemochi, Takemi

1996-01-01

The 2nd Department of Oral and Maxillofacial Surgery, Faculty of Dentistry Hospital, Iwate Medical University has performed radiation-combined intra-arterial chemotherapy as a preoperative treatment and subsequent mandibulectomy. During a 20 year-period from 1975 to 1994, clinical and histopathological examination of the above therapy was made for its effect and usefulness by using 15 primary cases of mandibular gingival squamous cell carcinoma, which were all identifiable. Roentgenological examination by bone resorptive pattern (invasive type, erosive type) and by bone resorptive depth (degree 0-III) revealed that early infiltration case and advanced case were predominant in the erosive type and the invasive type respectively. Histopathologically, the therapeutical effect of the radiation-combined intra-arterial chemotherapy on the tumor cells was examined using osteoclast, fibrous connective tissue, osteoblast, new bone, site of neoosteogenesis, and post-treatment site of residual tumor ceils as findings in the healing process. The histological therapeutic effect was good on well-differentiated type cases, and the histological effect on osteo-infiltrated region was as good as, or better than on soft tissue region. The cases with good histological therapeutic effect scarcely showed osteoclast, but showed remarkable hyperplasia of fibrous connective tissue, appearance of osteoblast and repair mechanism via neoosteogenesis. Invasive type tumor was persistent in the depth of the mandible, while erosive type tumor showed a tendency to be persistent in superficial layer. The results suggested that the application of the present radiation-combined intra-arterial chemotherapy to mandibular gingival squamous cell carcinoma is very useful leading to the improvement in radical curability of the tumor in its primary focus and the preservation of mandibular continuity in surgery. (author)

Severe antiphospholipid antibody syndrome - response to plasmapheresis and rituximab.

Science.gov (United States)

Gkogkolou, Paraskevi; Ehrchen, Jan; Goerge, Tobias

2017-09-01

Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disease characterized by arterial and/or venous thrombosis, recurrent abortions and detection of antiphospholipid antibodies. In fulminant cases, involvement of multiple organs can lead to significant morbidity and even fatal outcomes, so that a rapid, interdisciplinary treatment is needed. Here, we describe the case of a 39-year-old woman with a severe hard-to-treat APS with arterial occlusion and progressive skin necrosis, who was successfully treated with a combination therapy with plasmapheresis and rituximab. The treatment led to complete remission of the skin lesions for over a year. Clinical response correlated with a long-lasting reduction of antiphospholipid antibodies and B-cell depletion. This case demonstrates the use of antiphospholipid antibodies for monitoring APS-activity and shows that this severe vascular disease requires rigorous therapeutic approaches.

Intra-arterial chemotherapy combined with irradiation for invasive bladder cancer

International Nuclear Information System (INIS)

Fujimoto, Naohiro; Sato, Hideki; Harada, Shuji; Matsumoto, Tetsuro; Ikuyama, Toshihiro

2004-01-01

Total cystectomy and urinary diversion are the standard treatments for invasive bladder cancer. However, total cystectomy is not possible in some patients due to advanced age, a poor general condition, or refusal to undergo cystectomy. In such cases, intra-arterial chemotherapy (IAC) and/or radiotherapy are the alternative treatments. We performed IAC with cisplatin and adriamycin in 9 patients with invasive bladder cancer and obtained complete response (CR) in 5 out of the 9 patients (55.6%). However, 3 of these 5 CR patients developed local recurrence within 1 year. In an effort to improve the efficacy, we performed combination therapy comprising IAC plus radiotherapy in 12 patients with invasive bladder cancer. CR was obtained in 58.3% and the bladder was preserved in 91.7% with this combination therapy. However, distant metastases developed in 33.3% after the combined treatment of IAC plus radiation therapy. These findings suggest that the combination of radiotherapy and IAC is useful for local control of invasive bladder cancer. Data from more cases and results from a longer follow-up are needed to fully confirm the efficacy of this type of treatment. In addition, therapeutic modalities to prevent distant metastasis need to be considered. (author)

Combined chemotherapy and radiotherapy in the treatment of lung cancer

International Nuclear Information System (INIS)

Wolf, M.

1992-01-01

In the past decade the prognosis of patients with locally advanced lung cancer has not been altered significantly. In both small and non-small cell lung cancer cure rates are poor and 5-year survival rate still has not exceeded the 5% borderline. Despite of initially high response rates, a vast majority of patients suffered from tumor progression within 2 years after the start of treatment. Sites of tumor progression are either the primary tumor or the occurrence of distant metastases. Therefore, improvements of both local and systemic tumor control are necessary to increase long-term survival rate in lung cancer. Combined chemo- and radiotherapy may be an appropriate treatment approach to reach these aims. In patients with locally advanced lung cancer combined chemo-radiotherapy aims at overcoming radio- and chemo-therapy resistance as a cause of local treatment failure and at early eradication of distant micrometastases as a cause of systemic treatment failure. (author). 29 refs., 2 figs., 6 tabs

Phase III Randomized Study of Rituximab/Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) Compared With Iodine-131 Tositumomab/BEAM With Autologous Hematopoietic Cell Transplantation for Relapsed Diffuse Large B-Cell Lymphoma: Results From the BMT CTN 0401 Trial

Science.gov (United States)

Vose, Julie M.; Carter, Shelly; Burns, Linda J.; Ayala, Ernesto; Press, Oliver W.; Moskowitz, Craig H.; Stadtmauer, Edward A.; Mineshi, Shin; Ambinder, Richard; Fenske, Timothy; Horowitz, Mary; Fisher, Richard; Tomblyn, Marcie

2013-01-01

Purpose This clinical trial evaluated standard-dose radioimmunotherapy with a chemotherapy-based transplantation regimen followed by autologous hematopoietic cell transplantation versus rituximab with the same regimen in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients with chemotherapy-sensitive persistent or relapsed DLBCL were randomly assigned to receive iodine-131 tositumomab (dosimetric dose of 5 mCi on day −19 and therapeutic dose of 0.75 Gy on day −12), carmustine 300 mg/m2 (day −6), etoposide 100 mg/m2 twice daily (days −5 to −2), cytarabine 100 mg/m2 twice daily (days −5 to −2), and melphalan 140 mg/m2 (day −1; B-BEAM) or rituximab 375 mg/m2 on days −19 and −12 and the same chemotherapy regimen (R-BEAM). Results Two hundred twenty-four patients were enrolled, with 113 patients randomly assigned to R-BEAM and 111 patients assigned to B-BEAM. Two-year progression-free survival (PFS) rates, the primary end point, were 48.6% (95% CI, 38.6% to 57.8%) for R-BEAM and 47.9% (95% CI, 38.2% to 57%; P = .94) for B-BEAM, and the 2-year overall survival (OS) rates were 65.6% (95% CI, 55.3% to 74.1%) for R-BEAM and 61% (95% CI, 50.9% to 69.9%; P = .38) for B-BEAM. The 100-day treatment-related mortality rates were 4.1% (95% CI, 0.2% to 8.0%) for R-BEAM and 4.9% (95% CI, 0.8% to 9.0%; P = .97) for B-BEAM. The maximum mucositis score was higher in the B-BEAM arm (0.72) compared with the R-BEAM arm (0.31; P < .001). Conclusion The B-BEAM and R-BEAM regimens produced similar 2-year PFS and OS rates for patients with chemotherapy-sensitive relapsed DLBCL. No differences in toxicities other than mucositis were noted. PMID:23478060

Phase II study of gemcitabine plus cisplatin chemotherapy combined with intensity modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Ou Dan; He Xiayun; Hu Chaosu; Ying Hongmei; Zhu Guopei

2012-01-01

Objective: To evaluate the efficacy and toxicity of gemcitabine plus cisplatin (GP) chemotherapy combined with intensity-modulated radiation therapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: 71 patients (Stage III: 41, Stage IV A : 30) with locoregionally advanced NPC were entered this study. Neoadjuvant chemotherapy was consisted of cisplatin 25 mg/m 2 intravenously on d1-3 and gemcitabine 1000 mg/m 2 in 30 minutes intravenous infusion on days 1 and 8, every 3 weeks for 2 cycles. Adjuvant chemotherapy consisted of 2 cycles of the same GP regimen was given at 28 days after the end of radiotherapy. The prescription doses was 66.0-70.4 Gy to the gross tumor volume, 66 Gy to positive neck nodes, 60 Gy to the high-risk clinical target volume, 54 Gy to the low-risk clinical target volume. Results: The overall response rate to neoadjuvant chemotherapy was 91.2%, acute toxicity was mainly grade 1-2 myleosuppression. All patients completed IMRT. The median follow-up duration was 38 months. The 3-year nasopharyngeal local control, regional control, distant metastasis-free survival rate and overall survival rate were 93%, 99%, 91%, 90%, respectively. Severe late toxicities included grade 3 trismus in 1 patient, grade 3 hearing impairment in 2 patients and cranial nerve palsy in 2 patients, respectively. No grade 4 late toxicities were observed. Conclusions: The combination of GP chemotherapy and IMRT for locoregionally advanced nasopharyngeal carcinoma is well-tolerated, convenient, effective, and warrants further studies of more proper cycles of GP regimen. (authors)

Metronomic chemotherapy.

Science.gov (United States)

Mutsaers, Anthony J

2009-08-01

Chemotherapy drugs are usually administered at doses that are high enough to result in an obligatory break period to allow for the observation of potential side effects and institution of supportive care, if required. In recent years, efforts to administer chemotherapy on a more continuous basis, with a much shorter break period, or none at all, have received increased interest, and the practice has come to be known as metronomic chemotherapy. The basis for success with this currently investigational approach may be rooted in continuous drug exposure to susceptible cancer cells, inhibition of tumor blood vessel growth-a process known as tumor angiogenesis, and/or alterations in tumor immunology. Increased benefit also appears to occur when metronomic chemotherapy is used in combination with newer, targeted antiangiogenic agents, and therefore represents a promising approach to combination therapy, particularly as targeted oncology drugs make their way into veterinary oncology applications. There is still much to be learned in this field, especially with regard to optimization of the proper drugs, dose, schedule, and tumor applications. However, the low cost, ease of administration, and acceptable toxicity profiles potentially associated with this therapeutic strategy make metronomic chemotherapy protocols attractive and suitable to veterinary applications. Preliminary clinical trial results have now been reported in both human and veterinary medicine, including adjuvant treatment of canine splenic hemangiosarcoma and incompletely resected soft tissue sarcoma, and, further, more powerful studies are currently ongoing.

Efficacy of rituximab and plasmapharesis in an adult patient with antifactor H autoantibody-associated hemolytic uremic syndrome

Science.gov (United States)

Deville, Clemence; Garrouste, Cyril; Coppo, Paul; Evrard, Bertrand; Lautrette, Alexandre; Heng, Anne Elisabeth

2016-01-01

Abstract Antifactor H antibody (anti-CFHAb) is found in 6% to 25% cases of atypical hemolytic uremic syndrome (aHUS) in children, but has been only exceptionally reported in adults. There is no consensus about the best treatment for this type of aHUS. We report the case of an adult patient treated successfully with plasma exchange (PE), steroids, and rituximab. A 27-year-old Caucasian male presented to hospital with anemia, thrombocytopenia, and acute renal failure. One week earlier, he had digestive problems with diarrhea. The diagnosis of anti-CFHAb-associated aHUS (82,000 AU/mL) without CFHR gene mutations was established. He received Rituximab 375 mg/m2 (4 pulses) with PE and steroids. This treatment achieved renal and hematological remission at day (D) 31 and negative anti-CFHAb at D45 (<100 AU/mL). At D76, a fifth rituximab pulse was performed while CD19 was higher than 10/mm3. Steroids were stopped at month (M) 9. The patient has not relapsed during long-term follow-up (M39). Rituximab therapy can be considered for anti-CFHAb-associated aHUS. Monitoring of anti-CFHAb titer may help to guide maintenance therapeutic strategies including Rituximab infusion. PMID:27684863

Rituximab does not reset defective early B cell tolerance checkpoints

Science.gov (United States)

Chamberlain, Nicolas; Massad, Christopher; Oe, Tyler; Cantaert, Tineke; Herold, Kevan C.; Meffre, Eric

2015-01-01

Type 1 diabetes (T1D) patients show abnormalities in early B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive B cells in their blood. Treatment with rituximab, an anti-CD20 mAb that depletes B cells, has been shown to preserve β cell function in T1D patients and improve other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. However, it remains largely unknown how anti–B cell therapy thwarts autoimmunity in these pathologies. Here, we analyzed the reactivity of Abs expressed by single, mature naive B cells from 4 patients with T1D before and 52 weeks after treatment to determine whether rituximab resets early B cell tolerance checkpoints. We found that anti–B cell therapy did not alter the frequencies of autoreactive and polyreactive B cells, which remained elevated in the blood of all patients after rituximab treatment. Moreover, the limited proliferative history of autoreactive B cells after treatment revealed that these clones were newly generated B cells and not self-reactive B cells that had escaped depletion and repopulated the periphery through homeostatic expansion. We conclude that anti–B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti–B cell therapy. PMID:26642366

The use of anthracycline at first-line compared to alkylating agents or nucleoside analogs improves the outcome of salvage treatments after relapse in follicular lymphoma The REFOLL study by the Fondazione Italiana Linfomi.

Science.gov (United States)

Rossi, Giuseppe; Marcheselli, Luigi; Dondi, Alessandra; Bottelli, Chiara; Tucci, Alessandra; Luminari, Stefano; Arcaini, Luca; Merli, Michele; Pulsoni, Alessandro; Boccomini, Carola; Puccini, Benedetta; Micheletti, Moira; Martinelli, Giovanni; Rossi, Andrea; Zilioli, Vittorio Ruggero; Bozzoli, Valentina; Balzarotti, Monica; Bolis, Silvia; Cabras, Maria Giuseppina; Federico, Massimo

2015-01-01

Follicular lymphoma (FL) patients experience multiple remissions and relapses and commonly receive multiple treatment lines. A crucial question is whether anthracyclines should be used at first-line or whether they would be better "reserved" for relapse and whether FL outcome can be optimized by definite sequences of treatments. Randomized trials can be hardly designed to address this question. In this retrospective multi-institutional study, time-to-next-treatment after first relapse was analyzed in 510 patients who had received either alkylating agents- or anthracycline- or nucleoside analogs-based chemotherapy with/without rituximab at first-line and different second-line therapies. After a median of 42 months, median time-to-next-treatment after relapse was 41 months (CI95%:34-47 months). After adjustment for covariates, first-line anthracycline-based chemotherapy with/without rituximab was associated with better time-to-next-treatment after any salvage than alkylating agents-based chemotherapy with/without rituximab or nucleoside analogs-based chemotherapy with/without rituximab (HR:0.74, P = 0.027). The addition of rituximab to first-line chemotherapy had no significant impact (HR:1.22, P = 0.140). Autologs stem cell transplantation performed better than any other salvage treatment (HR:0.53, P < 0.001). First-line anthracycline-based chemotherapy significantly improved time-to-next-treatment even in patients receiving salvage autologs stem cell transplantation (P = 0.041). This study supports the concept that in FL previous treatments significantly impact on the outcome of subsequent therapies. The outcome of second-line treatments, either with salvage chemoimmunotherapy or with autologs stem cell transplantation, was better when an anthracycline-containing regimen was used at first-line. © 2014 Wiley Periodicals, Inc.

Acute emesis: moderately emetogenic chemotherapy

DEFF Research Database (Denmark)

Herrstedt, Jørn; Rapoport, Bernardo; Warr, David

2011-01-01

This paper is a review of the recommendations for the prophylaxis of acute emesis induced by moderately emetogenic chemotherapy as concluded at the third Perugia Consensus Conference, which took place in June 2009. The review will focus on new studies appearing since the Second consensus conference...... receiving multiple cycles of moderately emetogenic chemotherapy will be reviewed. Consensus statements are given, including optimal dose and schedule of serotonin(3) receptor antagonists, dexamethasone, and neurokinin(1) receptor antagonists. The most significant recommendations (and changes since the 2004...... version of the guidelines) are as follows: the best prophylaxis in patients receiving moderately emetogenic chemotherapy (not including a combination of an anthracycline plus cyclophosphamide) is the combination of palonosetron and dexamethasone on the day of chemotherapy, followed by dexamethasone...

Treatment of rheumatoid arthritis with biologic DMARDS (Rituximab and Etanercept).

Science.gov (United States)

Gashi, Afrim A; Rexhepi, Sylejman; Berisha, Idriz; Kryeziu, Avni; Ismaili, Jehona; Krasniqi, Gezim

2014-01-01

To determine efficacy and safety of treatment with Rituximab and Etanercept plus Methotrexate in patients with active Rheumatoid Arthritis (RA), who had an inadequate response to nonbiologic DMARDS therapies and to explore the pharmacogenetics and pharmacodynamics of Rituximab and Etanercept in our populations. Study was done at Rheumatology Clinic of University Clinical Centre in Prishtina during 2009-2011 years. We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the study of long-term efficacy of Rituximab and Etanercept. Patients with active Rheumatoid Arthritis and an inadequate response to 1 or more non biologic DMARDS were randomized to receive intravenous Rituximab (1 course consisting of 2 infusions of 1.000 mg each -one group, and Etanercept 25 mg twice weekly -second group, but both groups with background MTX. The primary efficacy end point was a response on the ACR 20%, improvement criteria at 24 weeks, Secondary end points were responses on the ACR 50 and ACR 70, improvement criteria, the DAS 28, and EULAR response criteria at 24 weeks. During our investigations we treated 20 patients, 15 females and 5 males, in the treated group with RTX and 13 patients 8 females and 5 males in the treated group with ETN. Patients of group 1 and group 2 were of ages 37-69 years old and 19-69 years old (average 47-44) Most of the patients belong in 2nd and 3rd functional stage according to Steinbrocker. All ACR response parameters were significantly improved in RTX treated patients who also had clinically meaningful improvement in fatigue, disability and quality of life. Patients showed a trend less progression in radiographic end points. Most adverse events occurred with the first RTX infusion and were mild to moderate severity. At 24 weeks, a single course of RTX and ETN provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to 1 or more

Effect of Kanglaite combined with chemotherapy on myelosuppression, immune function and tumor markers levels in patients with breast cancer

Directory of Open Access Journals (Sweden)

Qi Pan

2017-09-01

Full Text Available Objective: To investigate the effect of Kanglaite combined with chemotherapy on myelosuppression, immune function and tumor markers levels in patients with breast cancer. Methods: A total of 90 breast cancer patients in our hospital were randomly divided into control group (45 cases and observation group (45 cases. The two groups received CAF chemotherapy, and the observation group was additionally given Kanglaite injection (200 mL/d for 2 weeks continuously. Both groups had chemotherapy for 6 courses. The effect on myelosuppression, immune function and tumor markers levels was detected and compared before and after treatment in two groups. Results: After treatment, myelosuppression was found in both groups, and the levels of leukocyte, hemoglobin and platelet decreased significantly compared with before treatment (P0.05, and the levels of immune function indexes (CD3+, CD4+, CD4+/ CD8+ of the observation group were significantly higher than those in the control group （P<0.05） . After treatment, the levels of two tumor markers (CEA, CA15-3 decreased significantly than before treatment in both groups (P<0.05, and the decrease amplitude in the observation group was higher than that in the control group (P<0.05. Conclusions: Kanglaite combined with chemotherapy has evident therapeutic effect on breast cancer. It can alleviate the myelosuppression caused by chemotherapy, improve immune function, and reduce the concentration of tumor markers in patients with breast cancer.

A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR).

Science.gov (United States)

Fervenza, Fernando C; Canetta, Pietro A; Barbour, Sean J; Lafayette, Richard A; Rovin, Brad H; Aslam, Nabeel; Hladunewich, Michelle A; Irazabal, Maria V; Sethi, Sanjeev; Gipson, Debbie S; Reich, Heather N; Brenchley, Paul; Kretzler, Matthias; Radhakrishnan, Jai; Hebert, Lee A; Gipson, Patrick E; Thomas, Leslie F; McCarthy, Ellen T; Appel, Gerald B; Jefferson, J Ashley; Eirin, Alfonso; Lieske, John C; Hogan, Marie C; Greene, Eddie L; Dillon, John J; Leung, Nelson; Sedor, John R; Rizk, Dana V; Blumenthal, Samuel S; Lasic, Lada B; Juncos, Luis A; Green, Dollie F; Simon, James; Sussman, Amy N; Philibert, David; Cattran, Daniel C

2015-01-01

Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria. Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with i.v. rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study. This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic

Testing of mechanisms of action of rituximab and clinical results in high-risk patients with aggressive CD20+ lymphoma

International Nuclear Information System (INIS)

Jezersek Novakovic, B.; Juznic Setina, T.; Vovk, M.; Kotnik, V.; Novakovic, S.

2007-01-01

Rituximab has been applied successfully in the treatment of indolent and aggressive CD20 positive B cell lymphomas, yet the exact in vivo mechanisms of its action have not been unambiguously explained. This study was therefore aimed to confirm the presumed major mechanisms of action of rituximab and concomitantly to assess the effectiveness of first-line chemo immunotherapy in high-risk patients with aggressive CD20 lymphomas. The activity of rituximab was tested in vitro on Raji and SU-DHL-4 cells using the cell proliferation assay and flow cytometry. In the clinical part of the study, 20 high-risk patients with aggressive CD 20 lymphomas were treated with R-CHOP. Only complement-mediated cytotoxicity was observed under the in vitro applied experimental conditions. Neither the direct apoptotic effect nor the antibody-dependent cell-mediated cytotoxicity was detected probably due to a too low concentration of rituximab and a too low ratio of cytotoxic lymphocytes to tumor cells. The treatment outcome in patients was excellent since complete remissions were achieved in 90% of poor-risk patients at the end of primary treatment and 80% of patients were disease-free at 18.5 months median observation period. According to our results, the complement-dependent cytotoxicity is an important mechanism of rituximab action in vitro. To achieve direct apoptosis, higher concentrations than 20 μg/ml of rituximab should be used, while for an effective antibody-dependent cell-mediated cytotoxicity, the ratio of cytotoxic lymphocytes to tumor cells should be higher than 1:1. In the high-risk patients with aggressive CD20 lymphomas, the addition of rituximab to CHOP substantially improves the therapeutic results. (author)

Microwave Ablation in Combination with Chemotherapy for the Treatment of Advanced Non-Small Cell Lung Cancer

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Wei, Zhigang, E-mail: weizhigang321321@163.com; Ye, Xin, E-mail: yexintaian@aliyun.com; Yang, Xia, E-mail: yangxjinan@163.com; Zheng, Aimin, E-mail: am-zheng@163.com; Huang, Guanghui, E-mail: hgh3612@163.com; Li, Wenhong, E-mail: wenghong-li@163.com; Ni, Xiang, E-mail: asuka2521@hotmail.com; Wang, Jiao; Han, Xiaoying, E-mail: mylittlecarol@sina.com [Shandong Provincial Hospital Affiliated to Shandong University, Department of Oncology (China)

2015-02-15

PurposeTo verify whether microwave ablation (MWA) used as a local control treatment had an improved outcome regarding advanced non-small cell lung cancer (NSCLC) when combined with chemotherapy.MethodsThirty-nine patients with histologically verified advanced NSCLC and at least one measurable site other than the ablative sites were enrolled. Primary tumors underwent MWA followed by platinum-based doublet chemotherapy. Modified response evaluation criteria in solid tumors (mRECIST) and RECIST were used to evaluate therapeutic response. Complications were assessed using the National Cancer Institute Common Toxicity Criteria (version 3.0).ResultsMWA was administered to 39 tumors in 39 patients. The mean and median diameters of the primary tumor were 3.84 cm and 3.30 cm, respectively, with a range of 1.00–9.00 cm. Thirty-three (84.6 %) patients achieved a partial response. No correlation was found between MWA efficacy and clinicopathologic characteristics. For chemotherapy, 11 patients (28.2 %) achieved a partial response, 18 (46.2 %) showed stable disease, and 10 (25.6 %) had progressive disease. The overall objective response rate and disease control rate were 28.2 and 74.4 %, respectively. The median progression-free survival time was 8.7 months (95 % CI 5.5–11.9). The median overall survival time was 21.3 months (95 % CI 17.0–25.4). Complications were observed in 22 (56.4 %) patients, and grade 3 adverse events were observed in 3 (7.9 %) patients.ConclusionsPatients with advanced NSCLC could benefit from MWA in combination with chemotherapy. Complications associated with MWA were common but tolerable.

The effect of icotinib combined with chemotherapy in untreated non-small-cell lung cancer that harbored EGFR-sensitive mutations in a real-life setting: a retrospective analysis.

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Wang, Lulu; Li, Yan; Li, Luchun; Wu, Zhijuan; Yang, Dan; Ma, Huiwen; Wang, Donglin

2018-01-01

This study was conducted to compare the efficacy of a combination of icotinib and chemotherapy with icotinib or chemotherapy alone in untreated non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR)-sensitive mutations and to analyze the curative effect of different treatments on different genetic mutations (EGFR 19 exon deletion and L858R mutation) in a real-life setting. One hundred ninety-one patients were studied in this retrospective analysis from January 2013 to December 2015. The baseline characteristics, curative effects and adverse events of patients were analyzed. The primary endpoint was progression free survival (PFS). Longer PFS and overall survival (OS), and better objective response rate (ORR) were observed in the combination group compared to icotinib or chemotherapy along. For patients with an EGFR 19 exon deletion, the PFS, OS, and ORR in the combination group were superior to those in the icotinib or chemotherapy group. For the patients with the EGFR L858R mutation, better PFS and ORR were observed in the combination group, but OS was not obviously prolonged. Grade 3 or 4 adverse events were most commonly reported with combination therapy or chemotherapy alone. No possible drug-related interstitial lung disease or of drug related deaths occurred. The combination of icotinib and chemotherapy in patients with untreated NSCLC harboring sensitive EGFR mutations resulted in improved PFS and OS, especially in those who harbored the EGFR exon 19 deletion.

Clinical effect of systemic chemotherapy combined with transcatheter arterial chemoembolization in treatment of breast cancer with liver metastases

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LI Liye

2016-01-01

Full Text Available ObjectiveTo investigate the clinical effect of systemic chemotherapy combined with transcatheter arterial chemoembolization (TACE in the treatment of breast cancer with liver metastases. MethodsA total of 86 female breast cancer patients with liver metastases who were treated in the Affiliated Hospital of Shandong Academy of Medical Sciences from December 2012 to December 2014 were selected and equally divided into experimental group and control group. The patients in the control group received systemic chemotherapy, and those in the experimental group received systemic chemotherapy combined with TACE. The clinical effect, changes in lesions, and patients′ quality of life (QOL scores after treatment were compared between two groups. The t-test was applied for comparison of continuous data between the two groups, and the chi-square test was applied for comparison of categorical data between the two groups. ResultsThe experimental group had a significantly higher overall response rate than the control group (90.70% vs 58.14%, χ2=13.07, P=0.001. Compared with the control group, the experimental group had significantly smaller diameters of tumors and lymph nodes after treatment (t=4.26 and 4.63, both P＜0.001, as well as significantly higher QOL scores at 3 and 6 months after treatment (t=6.30 and 3.89, both P＜0001. ConclusionSystemic chemotherapy combined with TACE has a significant therapeutic effect in breast cancer patients with liver metastases, and can improve patients′ symptoms, reduce adverse drug reactions, and improve QOL. As a safe and reliable therapeutic method, it is worthy of clinical application.

Cost-Effectiveness Analysis of Bendamustine Plus Rituximab as a First-Line Treatment for Patients with Follicular Lymphoma in Spain.

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Sabater, Eliazar; López-Guillermo, Armando; Rueda, Antonio; Salar, Antonio; Oyagüez, Itziar; Collar, Juan Manuel

2016-08-01

Follicular lymphoma (FL) is the second most common type of lymphoid cancer in Western Europe. The aim of this study was to evaluate the cost utility of rituximab-bendamustine treatment compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) treatment as a first-line therapy for patients with advanced FL in Spain. A Markov model was developed to estimate the cost effectiveness of rituximab-bendamustine compared with R-CHOP as first-line treatment for patients with advanced FL in the Spanish National Health System (NHS). Transitions between health states (progression-free, including induction and maintenance; first relapse; second relapse; and death) were allowed for the patient cohort in 4-week-long cycles. Clinical data for the extrapolation of progression-free survival curves were obtained from randomized trials. Mortality rates and utilities were obtained from the literature. Outcomes were measured as quality-adjusted life-years (QALYs). The total costs (€, 2013) included drug costs (ex-factory prices with mandatory deductions), disease management costs and adverse event-associated costs. Costs and outcomes were discounted at a 3 % annual rate. Probabilistic sensitivity analysis was performed using 10,000 Monte Carlo simulations to assess the model robustness. Treatment and administration costs during the induction phase were higher for rituximab-bendamustine (€17,671) than for R-CHOP (€11,850). At the end of the 25-year period, the rituximab-bendamustine first-line strategy had a total cost of €68,357 compared with €69,528 for R-CHOP. Health benefits were higher for rituximab-bendamustine treatment (10.31 QALYs) than for R-CHOP treatment (9.82 QALYs). In the probabilistic analysis, rituximab-bendamustine was the dominant strategy over treatment with R-CHOP in 53.4 % of the simulations. First-line therapy with rituximab-bendamustine in FL patients was the dominant strategy over treatment with R-CHOP; it showed cost

Assessment of Physicochemical Properties of Rituximab Related to Its Immunomodulatory Activity

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Mariana P. Miranda-Hernández

2015-01-01

Full Text Available Rituximab is a chimeric monoclonal antibody employed for the treatment of CD20-positive B-cell non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis. It binds specifically to the CD20 antigen expressed on pre-B and consequently on mature B-lymphocytes of both normal and malignant cells, inhibiting their proliferation through apoptosis, CDC, and ADCC mechanisms. The immunomodulatory activity of rituximab is closely related to critical quality attributes that characterize its chemical composition and spatial configuration, which determine the recognition of CD20 and the binding to receptors or factors involved in its effector functions, while regulating the potential immunogenic response. Herein, we present a physicochemical and biological characterization followed by a pharmacodynamics and immunogenicity study to demonstrate comparability between two products containing rituximab. The physicochemical and biological characterization revealed that both products fit within the same response intervals exhibiting the same degree of variability. With regard to clinical response, both products depleted CD20+ B-cells until posttreatment recovery and no meaningful differences were found in their pharmacodynamic profiles. The evaluation of anti-chimeric antibodies did not show differential immunogenicity among products. Overall, these data confirm that similarity of critical quality attributes results in a comparable immunomodulatory activity.

Chemotherapy for head and neck cancer

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Pfister, David G.

1997-01-01

Purpose/Objective: The role of chemotherapy in the management of squamous cell carcinoma of the upper aerodigestive tract is undergoing rapid evolution. Historically, the use of chemotherapy was limited to patients with incurable disease who had exhausted all surgical and radiation therapy options. The results of recent randomized trials, however, suggest an increasing role for chemotherapy as part of primary management in patients with unresectable disease; advanced larynx or hypopharynx cancer with the intent of larynx preservation, or advanced nasopharynx cancer. This refresher course will provide a comprehensive overview of the current indications for chemotherapy in the management of these malignancies, and will highlight areas of controversy and future directions of investigation. More specifically, the following areas will be emphasized. 1. The identification of drugs commonly used in the management of head and neck cancer, their customary dosing and side effects. 2. The impact of induction and/or adjuvant chemotherapy combined with surgery and radiation therapy as defined by randomized trials, including a discussion of the Head and Neck Contracts program and the Intergroup adjuvant trial. 3. The development of larynx/function preservation treatment programs, including a review of the Veterans Administration and EORTC larynx preservation studies. 4. The evolving role of chemotherapy as part of innovative combined modality programs, especially in patients with unresectable disease. The rationale and utility of sequential versus concomitant/alternating chemotherapy-radiation strategies, and relevant randomized clinical trials comparing the different strategies will be discussed. 5. The appropriate application of chemotherapy in the palliative setting, including a discussion of the relative merits of single-agent versus combination chemotherapy

Chemotherapy for head and neck cancer

International Nuclear Information System (INIS)

Pfister, David G.

1995-01-01

Purpose/Objective: The role of chemotherapy in the management of squamous cell carcinoma of the upper aerodigestive tract is undergoing rapid evolution. Historically, the use of chemotherapy was limited to patients with incurable disease who had exhausted all surgical and radiation therapy options. The results of recent randomized trials, however, suggest an increasing role for chemotherapy as part of primary management in patients seeking to avoid potentially morbid surgical procedures or with unresectable disease. This refresher course will provide a comprehensive overview of the current indications for chemotherapy in the management of these malignancies, and will highlight areas of controversy and future directions of investigation. More specifically, the following areas will be emphasized. 1. The identification of drugs commonly used in the management of head and neck cancer, their customary dosing and side effects. 2. The impact of induction and/or adjuvant chemotherapy combined with surgery and radiation therapy as defined by randomized trials, including a discussion of the Head and Neck Contracts program and the Intergroup adjuvant trial. 3. The development of larynx/function preservation treatment programs, including a review of the Memorial Hospital experience with larynx preservation and the Veterans Administration larynx preservation study. 4. The evolving role of chemotherapy as part of innovative combined modality programs, especially in patients with unresectable disease. The rationale and utility of sequential versus concomitant/alternating chemotherapy-radiation strategies, and relevant randomized clinical trials comparing the different strategies will be discussed. 5. The appropriate application of chemotherapy in the palliative setting, including a discussion of the relative merits of single-agent versus combination chemotherapy

Standardization of Procedures for the Preparation of (177)Lu- and (90)Y-labeled DOTA-Rituximab Based on the Freeze-dried Kit Formulation.

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Wojdowska, Wioletta; Karczmarczyk, Urszula; Maurin, Michal; Garnuszek, Piotr; Mikołajczak, Renata

2015-01-01

Rituximab when radiolabelled with (177)Lu or (90)Y has been investigated for the treatment of patients with Non-Hodgkin's Lymphoma. In this study, we optimized the preparation of antibody conjugates with chelating agent in the freeze-dried kit. It shortens procedures needed for the successful radiolabeling with lutetium-177 and yttrium-90 and assures reproducible labelling yields. Various molar ratios of Rituximab:DOTA (from 1:5 to 1:100) were used at the conjugation step and different purification method to remove unbound DOTA were investigated (size-exclusion chromatography, dialysis, ultrafiltration). The final monoclonal antibody concentration was quantified by Bradford method, and the number of DOTA molecules was determined by radiolabeling assay using (64)Cu. The specific activity of (177)Lu-DOTA-Rituximab and (90)Y-DOTA-Rituximab were optimized using various amounts of radiometal. Quality control (SE-HPLC, ITLC) and stability study were performed. An average of 4.2 ± 0.8 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab. The ultrafiltration system was the most efficient for purification and resulted in the highest recovery efficiency (77.2%). At optimized conditions the (177)Lu-DOTARituximab and (90)Y-DOTA-Rituximab were obtained with radiochemical purity >99% and specific activity ca. 600 MBq/mg. The radioimmunoconjugates were stable in human serum and 0.9% NaCl. After 72 h of incubation the radiochemical purity of (177)Lu-DOTA-Rituximab decreased to 94% but it was still more than 88% for (90)Y-DOTA-Rituximab. The radioimmunoconjugate showed stability after six months storage at 2 - 8(0)C, as a lyophilized formulation. Our study shows that Rituximab-DOTA can be efficiently radiolabeled with (177)Lu and (90)Y via p-SCN-Bn-DOTA using a freezedried kit.

Comparable Efficacy of Idelalisib Plus Rituximab and Ibrutinib in Relapsed/refractory Chronic Lymphocytic Leukemia: A Retrospective Case Matched Study of the Polish Adult Leukemia Group (PALG).

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Puła, Bartosz; Budziszewska, Bożena Katarzyna; Rybka, Justyna; Gil, Lidia; Subocz, Edyta; Długosz-Danecka, Monika; Zawirska, Daria; Waszczuk-Gajda, Anna; Iskierka-Jażdżewska, Elżbieta; Kopacz, Agnieszka; Szymczyk, Agnieszka; Czyż, Jarosław; Lech-Marańda, Ewa; Warzocha, Krzysztof; Jamroziak, Krzysztof

2018-05-01

There is limited amount of data available on the comparative efficacy of ibrutinib and idelalisib, the B-cell receptor inhibitors (BCRi) newly approved for relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (r/r CLL/SLL) treatment. The aim of our study was to analyze and compare the outcomes of real-world r/r CLL/SLL patients treated with these two BCRi in outside clinical trials. A comparative case matched 1:2 analysis was performed on idelalisib combined with rituximab and ibrutinib efficacy in 102 patients with r/r CLL/SLL from two observational studies of the Polish Adult Leukemia Group (PALG). Both therapies produced similar overall response rates (idelalisib plus rituximab 76.4% and ibrutinib 72.1%). Median progression-free survival (PFS) and overall survival (OS) in both groups were not reached. Furthermore, no significant difference was observed between both BCRi regimens in regard to PFS (HR=0.75, 95% CI=0.30-1.86, p=0.55) and OS (HR=0.65, 95%CI=0.26-1.68, p=0.39). In summary, the results of this retrospective analysis suggest that idelalisib combined with rituximab and ibrutinib therapies have comparable activity in r/r CLL/SLL in daily clinical practice. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Combined Modality Treatment for PET-Positive Non-Hodgkin Lymphoma: Favorable Outcomes of Combined Modality Treatment for Patients With Non-Hodgkin Lymphoma and Positive Interim or Postchemotherapy FDG-PET

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Halasz, Lia M. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Jacene, Heather A. [Department of Imaging, Dana-Farber Cancer Institute, and Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Van den Abbeele, Annick D. [Department of Imaging, Dana-Farber Cancer Institute, and Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); LaCasce, Ann [Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Mauch, Peter M. [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Ng, Andrea K., E-mail: ang@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States)

2012-08-01

Purpose: To evaluate outcomes of patients treated for aggressive non-Hodgkin lymphoma (NHL) with combined modality therapy based on [{sup 18}F]fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) response. Methods and Materials: We studied 59 patients with aggressive NHL, who received chemotherapy and radiation therapy (RT) from 2001 to 2008. Among them, 83% of patients had stage I/II disease. Patients with B-cell lymphoma received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy, and 1 patient with anaplastic lymphoma kinase-negative anaplastic T-cell lymphoma received CHOP therapy. Interim and postchemotherapy FDG-PET or FDG-PET/computed tomography (CT) scans were performed for restaging. All patients received consolidated involved-field RT. Median RT dose was 36 Gy (range, 28.8-50 Gy). Progression-free survival (PFS) and local control (LC) rates were calculated with and without a negative interim or postchemotherapy FDG-PET scan. Results: Median follow-up was 46.5 months. Thirty-nine patients had negative FDG-PET results by the end of chemotherapy, including 12 patients who had a negative interim FDG-PET scan and no postchemotherapy PET. Twenty patients were FDG-PET-positive, including 7 patients with positive interim FDG-PET and no postchemotherapy FDG-PET scans. The 3-year actuarial PFS rates for patients with negative versus positive FDG-PET scans were 97% and 90%, respectively. The 3-year actuarial LC rates for patients with negative versus positive FDG-PET scans were 100% and 90%, respectively. Conclusions: Patients who had a positive interim or postchemotherapy FDG-PET had a PFS rate of 90% at 3 years after combined modality treatment, suggesting that a large proportion of these patients can be cured with consolidated RT.

Pre-emptive rituximab for Epstein-Barr virus reactivation after haplo-hematopoietic stem cell transplantation.

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Kobayashi, Shogo; Sano, Hideki; Mochizuki, Kazuhiro; Ohara, Yoshihiro; Takahashi, Nobuhisa; Ohto, Hitoshi; Kikuta, Atsushi

2017-09-01

Epstein-Barr virus-related post-transplantation lymphoproliferative disease (EBV-PTLD) is a serious complication in hematopoietic stem cell transplantation (HSCT) recipients. We conducted a retrospective study to investigate the incidence and potential risk factors for EBV reactivation and to assess the efficacy of the management of EBV reactivation with pre-emptive rituximab in children who had T-cell-replete haploidentical HSCT (TCR-haplo-SCT) with low-dose anti-thymocyte globulin (ATG). EBV-DNA level in peripheral blood (PB) was measured when suspected EBV reactivation were observed. When the EBV-DNA level in PB increased to >1,000 copies/10 6 peripheral blood mononuclear cells (PBMC), patients were pre-emptively treated with rituximab (375 mg/m 2 /dose). A total of 19 (50%) of 38 patients received rituximab infusion at a median time of 56 days after HSCT (range, 17-270 days). The median viral load at initiation of therapy was 2,900 copies/10 6 PBMC (range, 1,000-650 000). Pre-emptive therapy was started after a median of 2 days (range, 0-7 days). The median number of weekly treatment cycles was 2 (range, 1-3). None of the patients developed PTLD or other EBV-associated diseases. Pre-emptive rituximab therapy could be a useful strategy for EBV-PTLD in TCR-haplo-SCT recipients with low-dose ATG. © 2017 Japan Pediatric Society.

Neuromyelitis optica spectrum disorders: long-term safety and efficacy of rituximab in Caucasian patients.

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Radaelli, M; Moiola, L; Sangalli, F; Esposito, F; Barcella, V; Ferrè, L; Rodegher, M; Colombo, B; Fazio, R; Martinelli, V; Comi, G

2016-04-01

To assess the long-term benefit-risk profile of repeated courses of rituximab in Caucasian patients affected by neuromyelitis optica (NMO) and related disorders, in everyday clinical practice. This is a prospective observational study performed at San Raffaele Hospital, Milan, Italy. From February 2006, we recruited 21 patients affected by NMO and NMO spectrum of disorders (NMOSD) whom underwent at least one cycle of intravenous (i.v.) rituximab and then were followed for at least 2 years. At a mean follow-up time of 48 months, we observed a significant reduction of the annualized relapse rate (ARR), from 2.0 to 0.16 (p < 0.01); and of the median Expanded Disability Status Scale (EDSS), from 5.5 to 4.0 (p < 0.013). There were 12 patients (57%) who remained disease free during the follow-up period. Five patients (24%) reported mild hematological adverse events. Serious infectious adverse events were reported by another four patients: These were all wheelchair bound at the beginning of their rituximab treatment. A fixed treatment scheme of rituximab, with re-treatment every 6 months, was efficacious for NMO and NMOSD, with a good safety profile; however, to obtain an even better benefit-risk ratio, close monitoring of CD19(+) B cells should be performed before the re-treatment of patients with high-level disability, concomitant leukopenia and hypogammaglobulinemia. © The Author(s), 2015.

Influence of interventional chemotherapy combined with traditional Chinese medicine on the immune function of elderly patients with advanced lung cancer

International Nuclear Information System (INIS)

Jiang Tinghui; Wu Shiyan; Chen Yue; Zhang Qingquan; Zhang Weiwei; Shen Xubo; Wang Qianyao

2010-01-01

Objective: To investigate the influence of interventional chemotherapy combined with traditional Chinese medicine on the immune function in elderly patients with advanced lung cancer and to establish a comprehensive therapeutic pattern which is effective and economical with lower side-effects. Methods: A total of 60 aged patients with lung cancer were randomly and equally divided into two groups with 30 patients in each group. Patients in group A were purely treated with traditional Chinese medicine and patients in group B were treated with a combination of interventional chemotherapy and traditional Chinese medicine. And two therapeutic courses (6-8 weeks) were conducted in both groups. The serum T-lymphocyte subsets levels of CD3, CD4, CD8, CD4/CD8, NK cells and CD4 + CD25 + Treg cell levels were estimated with flow cytometry. The results were statistically analyzed. Results: No significant difference in serum levels of T cell subsets and CD4 + CD25 + Treg cell levels existed between the two groups, both before and after the treatment (P > 0.05). However, after the treatment the CD4 + CD25 + Treg cell level in group B was significantly lower than that in group A (P < 0.05). The short-term effective rate and the total clinical benefit rate in group B were 40% and 73.3% respectively, which were much better than those in group A (20% and 63.3% respectively). Conclusion: Interventional chemotherapy combined with traditional Chinese medicine will not damage the immune function of elderly patients with advanced lung cancer, on the contrary, the combination therapy, through effectively reducing the suppressor T cell level,shows excellent short-term effect. It indicates that interventional chemotherapy combined with Chinese medicine is an effective comprehensive therapeutic mode for elderly patients with advanced lung cancer. (authors)

Chemoimmunotherapy for Relapsed/Refractory and Progressive 17p13 Deleted Chronic Lymphocytic Leukemia (CLL) Combining Pentostatin, Alemtuzumab, and Low Dose Rituximab is Effective and Tolerable and Limits Loss of CD20 Expression by Circulating CLL Cells

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Zent, Clive S.; Taylor, Ronald P.; Lindorfer, Margaret A.; Beum, Paul V.; LaPlant, Betsy; Wu, Wenting; Call, Timothy G.; Bowen, Deborah A.; Conte, Michael J.; Frederick, Lori A.; Link, Brian K.; Blackwell, Sue E.; Veeramani, Suresh; Baig, Nisar A.; Viswanatha, David S.; Weiner, George J.; Witzig, Thomas E.

2014-01-01

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analogue refractory disease or TP53 dysfunction still have limited treatment options and poor survival. Alemtuzumab containing chemoimmunotherapy regimens can be effective but frequently cause serious infections. We report a phase II trial testing the efficacy and tolerability of a short duration regimen combining pentostatin, alemtuzumab, and low dose high frequency rituximab (PAR) designed to decrease the risk of treatment associated infections and limit loss of CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL that was either relapsed/refractory (n=36) or previously untreated with 17p13 deletion (17p13-)(n=3). Thirteen (33%) patients had both 17p13- and TP53 mutations predicted to be dysfunctional and eight patients had purine analogue refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed therapy with only five (13%) patients having treatment limiting toxicity, and no treatment related deaths. Twenty-two (56%) patients responded to treatment with 11 (28%) complete responses (four with incomplete bone marrow recovery). Median progression free survival was 7.2 months, time to next treatment 9.1 months, and overall survival 34.1 months. The majority of deaths (82%) were caused by progressive disease including transformed diffuse large B cell lymphoma (n=6). Correlative studies showed that low dose rituximab activates complement and NK cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that PAR is a tolerable and effective therapy for CLL and that low dose rituximab therapy can activate innate immune cytotoxic mechanisms without substantially decreasing CD20 expression. PMID:24723493

Epstein-Barr Virus-Negative Post-Transplant Lymphoproliferative Diseases: Three Distinct Cases from a Single Center

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Şule Mine Bakanay

2014-03-01

Full Text Available Three cases of Epstein-Barr virus (EBV-negative post-transplant lymphoproliferative disease that occurred 6 to 8 years after renal transplantation are reported. The patients respectively had gastric mucosa-associated lymphoid tissue lymphoma, gastric diffuse large B-cell lymphoma, and atypical Burkitt lymphoma. Absence of EBV in the tissue samples was demonstrated by both in situ hybridization for EBV early RNA and polymerase chain reaction for EBV DNA. Patients were treated with reduction in immunosuppression and combined chemotherapy plus an anti-CD20 monoclonal antibody, rituximab. Despite the reduction in immunosuppression, patients had stable renal functions without loss of graft functions. The patient with atypical Burkitt lymphoma had an abnormal karyotype, did not respond to treatment completely, and died due to disease progression. The other patients are still alive and in remission 5 and 3 years after diagnosis, respectively. EBV-negative post-transplant lymphoproliferative diseases are usually late-onset and are reported to have poor prognosis. Thus, reduction in immunosuppression is usually not sufficient for treatment and more aggressive approaches like rituximab with combined chemotherapy are required.

Microcosting Study of Rituximab Subcutaneous Injection Versus Intravenous Infusion

NARCIS (Netherlands)

Mihajloviç, Jovan; Bax, Pieter; van Breugel, Erwin; Blommestein, Hedwig M.; Hoogendoorn, Mels; Hospes, Wobbe; Postma, Maarten J.

Purpose: The goal of this study is to identify and compare all direct costs of intravenous and subcutaneous rituximab given to patients with diffuse large B-cell lymphoma in the Netherlands.  Methods: Using a prospective, observational, bottom-up microcosting study, we collected primary data on the

Nanotechnology for Cancer Therapy Based on Chemotherapy

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Chen-Yang Zhao

2018-04-01

Full Text Available Chemotherapy has been widely applied in clinics. However, the therapeutic potential of chemotherapy against cancer is seriously dissatisfactory due to the nonspecific drug distribution, multidrug resistance (MDR and the heterogeneity of cancer. Therefore, combinational therapy based on chemotherapy mediated by nanotechnology, has been the trend in clinical research at present, which can result in a remarkably increased therapeutic efficiency with few side effects to normal tissues. Moreover, to achieve the accurate pre-diagnosis and real-time monitoring for tumor, the research of nano-theranostics, which integrates diagnosis with treatment process, is a promising field in cancer treatment. In this review, the recent studies on combinational therapy based on chemotherapy will be systematically discussed. Furthermore, as a current trend in cancer treatment, advance in theranostic nanoparticles based on chemotherapy will be exemplified briefly. Finally, the present challenges and improvement tips will be presented in combination therapy and nano-theranostics.

Doxorubicin and ifosfamide combination chemotherapy in previously treated acute leukemia in adults: a Southwest Oncology Group pilot study.

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Ryan, D H; Bickers, J N; Vial, R H; Hussein, K; Bottomley, R; Hewlett, J S; Wilson, H E; Stuckey, W J

1980-01-01

The Southwest Oncology Group did a limited institutional pilot study of the combination of doxorubicin and ifosfamide in the treatment of previously treated adult patients with acute leukemia. Thirty-four patients received one or two courses of the combination. All patients had received prior chemotherapy and 32 had received prior anthracycline chemotherapy. Three patients died before their responses could be fully evaluated. Fourteen patients achieved complete remission (41%) and one patient achieved partial remission. The complete remission rate was 27% for patients with acute myeloblastic leukemia (myelomonoblastic leukemia, monoblastic leukemia, and erythroleukemia) and 89% for patients with acute lymphocytic and undifferentiated leukemia (ALL). Toxic effects included severe hematologic reactions in 33 of 34 patients, hematuria in six patients, altered sensorium in one patient, and congestive heart failure in one patient. The safety of the combination was established and toxic side effects of this therapy were tolerable. The 89% complete remission rate for previously treated patients with ALL suggests that the combination of doxorubicin and ifosfamide may be particularly effective in ALL.

Hyperthermia and chemotherapy agent

International Nuclear Information System (INIS)

Roizin-Towle, L.; Hall, E.J.

1981-01-01

The use of chemotherapeutic agents for the treatment of cancer dates back to the late 19th century, but the modern era of chemotherapy drugs was ushered in during the 1940's with the development of the polyfunctional alkylating agent. Since then, numerous classes of drugs have evolved and the combined use of antineoplastic agents with other treatment modalities such as radiation or heat, remains a large relatively unexplored area. This approach, combining local hyperthermia with chemotherapy agents affords a measure of targeting and selective toxicity not previously available for drugs. In this paper, the effects of adriamycin, bleomycin and cis-platinum are examined. The adjuvant use of heat may also reverse the resistance of hypoxic cells noted for some chemotherapy agents

The effect of icotinib combined with chemotherapy in untreated non-small-cell lung cancer that harbored EGFR-sensitive mutations in a real-life setting: a retrospective analysis

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Wang LL

2018-04-01

Full Text Available Lulu Wang, Yan Li, Luchun Li, Zhijuan Wu, Dan Yang, Huiwen Ma, Donglin Wang Oncology Department, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Shapingba District, Chongqing, China Purpose: This study was conducted to compare the efficacy of a combination of icotinib and chemotherapy with icotinib or chemotherapy alone in untreated non-small cell lung cancer (NSCLC patients harboring epidermal growth factor receptor (EGFR-sensitive mutations and to analyze the curative effect of different treatments on different genetic mutations (EGFR 19 exon deletion and L858R mutation in a real-life setting. Patients and methods: One hundred ninety-one patients were studied in this retrospective analysis from January 2013 to December 2015. The baseline characteristics, curative effects and adverse events of patients were analyzed. The primary endpoint was progression free survival (PFS. Results: Longer PFS and overall survival (OS, and better objective response rate (ORR were observed in the combination group compared to icotinib or chemotherapy along. For patients with an EGFR 19 exon deletion, the PFS, OS, and ORR in the combination group were superior to those in the icotinib or chemotherapy group. For the patients with the EGFR L858R mutation, better PFS and ORR were observed in the combination group, but OS was not obviously prolonged. Grade 3 or 4 adverse events were most commonly reported with combination therapy or chemotherapy alone. No possible drug-related interstitial lung disease or of drug related deaths occurred. Conclusion: The combination of icotinib and chemotherapy in patients with untreated NSCLC harboring sensitive EGFR mutations resulted in improved PFS and OS,especially in those who harbored the EGFR exon 19 deletion. Keywords: non-small-cell lung cancer, EGFR-TKI, icotinib, chemotherapy, first-line treatment

Overview of different available chemotherapy regimens combined with radiotherapy for the neoadjuvant and definitive treatment of esophageal cancer.

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Tomasello, Gianluca; Ghidini, Michele; Barni, Sandro; Passalacqua, Rodolfo; Petrelli, Fausto

2017-06-01

Neoadjuvant chemoradiotherapy (CTRT) is the current standard of care for treatment of locally advanced cancer of the esophagus or gastroesophageal junction. Many efforts have been made over the last years to identify the best chemotherapy and radiotherapy combination regimen, but specific randomized trials addressing this issue are still lacking. Areas covered: A systematic review of the literature was performed searching in PubMed all published studies of combinations CTRT regimens for operable or unresectable esophageal cancer to describe activity and toxicity. Studies considered were prospective series or clinical phase II-III trials including at least 40 patients and published in English language. Expert commentary: Long-term results of CROSS trial have established RT combined with carboplatin plus paclitaxel chemotherapy as the preferred neoadjuvant treatment option for both squamous and adenocarcinoma of the esophagus. More effective multimodal treatment strategies integrating novel biological agents including immunotherapy and based on an extensive molecular tumor characterization are eagerly awaited.

[Efficacy of granisetron for preventing chemotherapy-induced nausea and vomiting in patients with acute myelogenous leukemia treated with a combination of anthracycline and cytarabine].

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Goto, Takashi; Tanimoto, Kazuki; Ishibashi, Makoto; Okamura, Seiichi

2012-08-01

In Japan, the combination of anthracycline and cytarabine(Ara-C)is a standard therapy for acute myelogenous leukemia(AML). Chemotherapy-induced nausea and vomiting(CINV)are frequently reported as side effects related to the administration of these regimens. In our hospital, patients received prophylactic granisetron at a dose of 3 mg daily during chemotherapy. However, granisetron is known to induce constipation as a side effect. The present study evaluated the efficacy of a single dose of granisetron administered throughout the entire period of chemotherapy in AML patients receiving anthracycline and Ara-C combination therapy, and also examined the incidence of constipation during chemotherapy. From July 2008 to December 2010, all patients with AML treated using anthracycline and Ara-C combination therapy were registered in the study. This retrospective study investigated the patients' background and the incidence of CINV and constipation from the patients' records. The efficacy of granisetron was measured on each day using the complete regression(no vomiting and no rescue medication; CR)rate. A total of 45 patients were included in the study(27 male; 18 female), and received a total 68 courses(56 of induction therapy; 12 of consolidation therapy)of the regimens. The CR rate and the incidence of constipation on the final day of chemotherapy were 61. 8% and 63. 2%, respectively. As the duration of chemotherapy increased, the CR rate tended to decrease, whereas the incidence of constipation tended to increase. The CR rate in this study was 61. 8%, thus indicating that there is still room for improvement. The combination of dexamethasone and a neurokinin-1 receptor antagonist, or the changeover from granisetron to palonosetron could therefore increase the CR rate.

Chemokine/cytokine profiling after rituximab: reciprocal expression of BCA-1/CXCL13 and BAFF in childhood OMS.

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Pranzatelli, Michael R; Tate, Elizabeth D; Travelstead, Anna L; Verhulst, Steven J

2011-03-01

The aim of the study was to test the hypothesis that B-cell repopulation following rituximab (anti-CD20) therapy is orchestrated by chemokines and non-chemokine cytokines. Twenty-five children with opsoclonus-myoclonus syndrome (OMS) received rituximab with or without conventional agents. A comprehensive panel of 40 chemokines and other cytokines were measured in serum by ELISA and multiplexed fluorescent bead-based immunoassay. Serum BAFF concentration changed dramatically (even after first infusion) and inversely with B-cell depletion/repopulation and CXCL13 concentration at 1, 3, and 6 months. Negative correlations were found for BAFF concentration vs blood B cell percentage and serum CXCL13 concentration; positive correlations with serum rituximab concentrations. Six months after initiation of therapy, no significant difference in the levels of APRIL, CXCL10, IL-6, or 17 other cytokines/chemokines were detected. These data reveal a major role for BAFF in peripheral B cell repopulation following rituximab-induced B-cell depletion, and novel changes in CXCL13. ClinicalTrials.gov NCT0024436. Copyright © 2010 Elsevier Ltd. All rights reserved.

Immunological profile in cerebrospinal fluid of patients with multiple sclerosis after treatment switch to rituximab and compared with healthy controls.

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Pierre de Flon

Full Text Available To investigate changes in the cerebrospinal fluid (CSF immunological profile after treatment switch from first-line injectables to rituximab in patients with relapsing-remitting MS (RRMS, and to compare the profile in MS patients with healthy controls (HC.Cerebrospinal fluid from 70 patients with clinically stable RRMS and 55 HC was analysed by a multiplex electrochemiluminescence method for a broad panel of cytokines and immunoactive substances before, and over a two-year period after, treatment switch to rituximab. After quality assessment of data, using a predefined algorithm, 14 analytes were included in the final analysis.Ten of the 14 analytes differed significantly in MS patients compared with HC at baseline. Levels of IP-10 (CXCL10, IL-12/23p40, IL-6, sVCAM1, IL-15, sICAM1 and IL-8 (CXCL8 decreased significantly after treatment switch to rituximab. The cytokines IP-10 and IL-12/IL-23p40 displayed the largest difference versus HC at baseline and also the largest relative reduction after therapy switch to rituximab.We found significant changes in the immunological profile after therapy switch to rituximab in RRMS in the direction towards the values of HC. IP-10 and IL12/IL-23p40 deserve further studies as part of the immunopathogenesis of MS as well as for the mode of action of rituximab in MS.

Successful plasma exchange combined with rituximab therapy in aggressive APS-related cutaneous necrosis.

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Costa, Rubens; Fazal, Salman; Kaplan, Robert B; Spero, Joel; Costa, Ricardo

2013-03-01

Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disorder characterized by venous and/or arterial thrombosis or recurrent fetal loss associated with the presence of antiphospholipid antibodies and/or a lupus anticoagulant. The skin appears to be an important target organ and many cases of APS may present with skin manifestations. These lesions may be manifold and may take the form of livedo reticularis, livedo racemosa, ulcerations, digital gangrene, subungeal splinter hemorrhages, superficial venous thrombosis, thrombocytopenic purpura, pseudovasculitic manifestations, extensive cutaneous necrosis, or primary anetoderma. We report a case of fulminant APS-related cutaneous necrosis. A 38-year-old Caucasian male with a past history of APS, multiple deep vein thrombi/pulmonary emboli, presented with necrotic lesions on his right upper and right lower extremities. Initially, baseline anticoagulation was increased without improvement. Subsequently, plasma exchange was initiated on a daily schedule. Furthermore, rituximab 1,000 mg IV was administered on days 1 and 15. After six consecutive daily sessions of plasma exchange, there was significant regression of the necrotic lesions. After a 22-day hospital stay, the patient was discharged to home on fondaparinux. The patient presented approximately 2 months later after missing follow-up appointments. At the time, his initial lesions looked remarkably improved.

Adjuvant chemotherapy and cancer cure

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Bertino, J.R.

1983-01-01

The use of chemotherapy as an adjuvant to surgery and/or radiotherapy is well founded in experimental tumor systems and appears to be effective in patients in some circumstances. It is clear from both clinical and experimental studies that (1) the dose is important, (2) the earlier chemotherapy is started after primary therapy the better, and (3) combination chemotherapy may be more effective than single-agent treatment. The better the estimation of risk of recurrence, the better the assessment of the risk-benefit ratio with adjuvant therapy. Salvage therapy as well as relative risk of recurrence are considerations in the choice of patients to be treated. Finally, some evidence is presented to indicate that alkylating agents may not be necessary in combination regimens for adjuvant therapy if effective antimetabolite combinations are available

Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early stage Hodgkin lymphoma (Review)

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Blank, Oliver; von Tresckow, Bastian; Monsef, Ina

2017-01-01

BACKGROUND: Combined modality treatment consisting of chemotherapy followed by localised radiotherapy is the standard treatment for patients with early stage Hodgkin lymphoma (HL). However, due to long- term adverse effects such as secondary malignancies the role of radiotherapy has been questioned...... recently and some clinical study groups advocate chemotherapy only for this indication. OBJECTIVES: To assess the effects of chemotherapy alone compared to chemotherapy plus radiotherapy in adults with early stage HL . SEARCH METHODS: For the or i ginal version of this review, we searched MEDLINE, Embase......-related mortality (RR 0.99; 95% CI 0.14 to 6.90; P = 0.99; low-quality evidence), there is no evidence for a difference between the use of chemotherapy alone and chemotherapy plus radiotherapy. CRR rate was not reported. AUTHORS' CONCLUSIONS: This systematic review compared the effects of chemotherapy alone...

Long-Term Maintenance Therapy Using Rituximab-Induced Continuous B-Cell Depletion in Patients with ANCA Vasculitis

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Pendergraft, William F.; Cortazar, Frank B.; Wenger, Julia; Murphy, Andrew P.; Rhee, Eugene P.; Laliberte, Karen A.; Niles, John L.

2014-01-01

Background and objectives Remission in the majority of ANCA vasculitis patients is not sustained after a single course of rituximab, and risk of relapse warrants development of a successful strategy to ensure durable remission. Design, setting, participants, & measurements A retrospective analysis of ANCA vasculitis patients who underwent maintenance therapy using rituximab-induced continuous B-cell depletion for up to 7 years was performed. Maintenance therapy with rituximab was initiated after achieving remission or converting from other prior maintenance therapy. Continuous B-cell depletion was achieved in all patients by scheduled rituximab administration every 4 months. Disease activity, serologic parameters, adverse events, and survival were examined. Results In the study, 172 patients (mean age=60 years, 55% women, 57% myeloperoxidase–ANCA) treated from April of 2006 to March of 2013 underwent continuous B-cell depletion with rituximab. Median remission maintenance follow-up time was 2.1 years. Complete remission (Birmingham Vasculitis Activity Score [BVAS]=0) was achieved in all patients. Major relapse (BVAS≥3) occurred in 5% of patients and was associated with weaning of other immunosuppression drugs. Remission was reinduced in all patients. Survival mirrored survival of a general age-, sex-, and ethnicity-matched United States population. Conclusion This analysis provides evidence for long-term disease control using continuous B-cell depletion. This treatment strategy in ANCA vasculitis patients also seems to result in survival rates comparable with rates in a matched reference population. These findings suggest that prospective remission maintenance treatment trials using continuous B-cell depletion are warranted. PMID:24626432

Combined radiotherapy and chemotherapy for pediatric medulloblastoma: a clinical study of 33 cases

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Wei ZHENG

2011-06-01

Full Text Available Objective To retrospectively review the clinical characteristics of medulloblastoma,discuss the optimized treatment regimen,and analyze the prognostic influential factors.Methods Thirty-three children with pathologically certified medulloblastoma(aged 3-14 years with average of 6.5 years,admitted from Aug.2004 to Dec.2007,received radiotherapy within 3 weeks post surgery.Ratiotherapy consisted of 28~36Gy whole craniospinal radiation and a supplementary radiation aimed at tumors by three-dimensional conformal radiotherapy(3D-CRT for a total dose of 50~54Gy(conventional fraction dose of 1.8-2.0Gy.A part of patients received hyperfractionation radiotherapy(1.0Gy/f,2f/d for alleviating the tardive adverse events.Meanwhile,a synchronized chemotherapy,consisting of lomustine + vincristine + cisplatin,or isophosphamide + carboplatin + etoposide,was administered after the completion of whole craniospinal radiation,and 3-5 courses of sequential chemotherapy were given after the overall radiotherapy was finished.According to the metastasis,and the residual tumor and its size,the 33 patients were divided into 2 groups as follows: low-risk group(n=24: no metastases,total or sub-total excision of tumors(residual tumors ≤1.5cm3;high-risk group(n=9: either metastases or residual tumor > 1.5cm3.The 3-year survival rates of two groups were then compared.Results The combined radiotherapy and chemotherapy was effective to 10 of the 11 patients(90.9% with residual tumors.Out of the 33 patients,31 obtained complete remission(93.9%,and 2 patients showed partial remission or stable status(3.0%,respectively.The median survival time of 33 patients was 51 months,3-year disease free survival(DFS was 75.8%,and 3-year overall survival(OS was 78.8%,including 33.3% in high-risk group and 95.8% in low-risk group(P < 0.01.The major side effects occurred in haematological system and digestive system,such as an incidence of 21.2%(7/33 with grade Ⅲ-Ⅳ bone marrow suppression

Clinical Observation of Recombinant Human Vascular Endostatin Durative Transfusion Combined with Window Period Arterial Infusion Chemotherapy in the Treatment of 
Advanced Lung Squamous Carcinoma

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Yuan LV

2015-08-01

Full Text Available Background and objective Lung cancer is one of the most common malignant tumors in China. The aim of this study is to observe the efficacy and safety of recombinant human vascular endostatin (endostar durative transfusion combined with window period arterial infusion chemotherapy in the treatment of advanced lung squamous carcinoma. Methods From February 2014 to January 2015, 10 cases of the cytological or histological pathology diagnosed stage IIIb - stage IV lung squamous carcinoma were treated with recombinant human vascular endostatin (30 mg/d durative transfusion combined with window period arterial infusion chemotherapy. Over the same period of 10 cases stage IIIb - stage IV lung squamous carcinoma patients for pure arterial perfusion chemotherapy were compared. Recombinant human vascular endostatin was durative transfused every 24 hours for 7 days in combination group, and in the 4th day of window period, the 10 patients were received artery infusion chemotherapy, using docetaxel combined with cisplatin. Pure treatment group received the same arterial perfusion chemotherapy regimen. 4 weeks was a cycle. 4 weeks after 2 cycles, to evaluate the short-term effects and the adverse drug reactions. Results 2 groups of patients were received 2 cycles treatments. The response rate (RR was 70.0%, and the disease control rate (DCR was 90.0% in the combination group; In the pure treatment group were 50.0%, 70.0% respectively, there were no statistically significant difference (P=0.650, 0.582. The adverse reactions of the treatment were mild, including level 1-2 of gastrointestinal reaction and blood toxicity, there were no statistically significant difference (P=0.999, P=0.628. In the combination group, 1 patient occurred level 1 of cardiac toxicity. Conclusion Recombinant human vascular endostatin durative transfusion combined with window period arterial infusion chemotherapy in the treatment of advanced lung squamous carcinoma could take a

Crohn's disease complicated by Epstein-Barr virus-driven haemophagocytic lymphohistiocytosis successfully treated with rituximab.

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Thompson, Grace; Pepperell, Dominic; Lawrence, Ian; McGettigan, Benjamin David

2017-02-22

We report a case of Epstein-Barr virus (EBV)-driven haemophagocytic lymphohistiocytosis (HLH) in a man with Crohn's disease treated with 6-mercaptopurine and adalimumab therapy who was successfully treated with rituximab therapy alone. This is the first published case in an adult patient with EBV-driven HLH in the setting of thiopurine use and inflammatory bowel disease to be successfully treated with rituximab therapy alone. Here, we will discuss putative immunological mechanisms which may contribute to this potentially life-threatening complication. 2017 BMJ Publishing Group Ltd.

B-cell depletion with rituximab in the treatment of autoimmune diseases. Graves' ophthalmopathy the latest addition to an expanding family

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Nielsen, Claus H; El Fassi, Daniel; Hasselbalch, Hans K

2007-01-01

In this review, the authors summarise the clinical results obtained after therapy with rituximab in autoimmune diseases, including Graves' disease and Graves' ophthalmopathy. On the basis of qualitative and quantitative analyses of B- and T-cell subsets, and autoantibody levels obtained in other...... diseases before and after rituximab therapy, the authors interpret the results of the only two clinical investigations of the efficacy of rituximab in the treatment of Graves' disease and Graves' opthalmopathy reported so far. No significant effect on autoantibody levels was observed. Nonetheless, 4 out...... of 10 Graves' disease patients remained in remission 400 days after rituximab treatment versus none in the control group, and remarkable improvements in the eye symptoms of patients with Graves' ophthalmopathy were observed. This supports a role for B cells in the pathogenesis of Graves' ophthalmopathy...

Comparison of efficacy and tolerance between combination therapy and monotherapy as first-line chemotherapy in elderly patients with advanced gastric cancer: Study protocol for a randomized controlled trial.

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Lee, Keun-Wook; Zang, Dae Young; Ryu, Min-Hee; Kim, Ki Hyang; Kim, Mi-Jung; Han, Hye Sook; Koh, Sung Ae; Park, Jin Hyun; Kim, Jin Won; Nam, Byung-Ho; Choi, In Sil

2017-12-01

The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy. This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety. We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.

Rituximab (MabThera) til behandling af aktiv reumatoid artritis

DEFF Research Database (Denmark)

El Fassi, Daniel; Nielsen, Claus Henrik; Bendtzen, Klaus

2006-01-01

Rituximab (RTX) is a murine/human monoclonal antibody to CD20, a protein expressed almost exclusively on human B-lymphocytes. RTX induces rapid and marked B-cell depletion with beneficial clinical effects in 1/3 to 1/2 of rheumatoid arthritis patients. Treatment is given as two iv. infusions with...

Clinical and histopathological studies on the squamous cell carcinoma of the tongue treated with radiation-combined intra-arterial chemotherapy

International Nuclear Information System (INIS)

Hoshi, Hideki

2000-01-01

Because oral cancer treatment has advanced, resulting in a higher survival rate, it is necessary to treat the preserved oral functions such as speech, mastication, and deglutition, as well as the aesthetics. Oral cancer treatment has been performed mainly by surgical therapy and radiation therapy, however, integrated treatment including chemotherapy has recently been performed. In this study, we evaluated the effectiveness and usefulness of radiation-combined intra-arterial chemotherapy for carcinomas of the tongue, which shows a high incident rate among oral cancers and has become more common recently, to establish treatment methods for preserving the function and morphology. The subjects were 63 patients who consulted our department and underwent radiation-combined intra-arterial chemotherapy. With this therapy, the case of complete response (CR) was clinically obtained in 43 patients, and the case of partial response (PR) was obtained in 17 patients with a 68.3% CR rate and a 95.2% therapeutic effectiveness rate. Maintenance therapy was performed in 44 patients without performing surgical therapy of the primary lesion in the primary treatment. Twenty-nine among 44 patients showed a good clinical course without recurrence of primary lesion. Regarding T4, a good clinical course without recurrence was observed in 3 patients in which PR was obtained, and surgical therapy was added to the primary treatment, showing a 57.1% local control rate in T4. Considering these results, there is a high possibility that radiation-combined intra-arterial chemotherapy for carcinomas of the tongue can be implemented for avoiding surgical therapy of the primary lesion in the primary treatment, and it is useful for preserving the function and morphology with a high local control rate. (author)

Clinical and histopathological studies on the squamous cell carcinoma of the tongue treated with radiation-combined intra-arterial chemotherapy

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Hoshi, Hideki [Iwate Medical Coll., Morioka (Japan). School of Dentistry

2000-12-01

Because oral cancer treatment has advanced, resulting in a higher survival rate, it is necessary to treat the preserved oral functions such as speech, mastication, and deglutition, as well as the aesthetics. Oral cancer treatment has been performed mainly by surgical therapy and radiation therapy, however, integrated treatment including chemotherapy has recently been performed. In this study, we evaluated the effectiveness and usefulness of radiation-combined intra-arterial chemotherapy for carcinomas of the tongue, which shows a high incident rate among oral cancers and has become more common recently, to establish treatment methods for preserving the function and morphology. The subjects were 63 patients who consulted our department and underwent radiation-combined intra-arterial chemotherapy. With this therapy, the case of complete response (CR) was clinically obtained in 43 patients, and the case of partial response (PR) was obtained in 17 patients with a 68.3% CR rate and a 95.2% therapeutic effectiveness rate. Maintenance therapy was performed in 44 patients without performing surgical therapy of the primary lesion in the primary treatment. Twenty-nine among 44 patients showed a good clinical course without recurrence of primary lesion. Regarding T4, a good clinical course without recurrence was observed in 3 patients in which PR was obtained, and surgical therapy was added to the primary treatment, showing a 57.1% local control rate in T4. Considering these results, there is a high possibility that radiation-combined intra-arterial chemotherapy for carcinomas of the tongue can be implemented for avoiding surgical therapy of the primary lesion in the primary treatment, and it is useful for preserving the function and morphology with a high local control rate. (author)

Dosimetric analysis of 177Lu-DOTA-rituximab in patients with relapsed/refractory non-Hodgkin's lymphoma.

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Yadav, Madhav P; Singla, Suhas; Thakral, Parul; Ballal, Sanjana; Bal, Chandrasekhar

2016-07-01

Radioimmunotherapy targeting CD20 receptors in lymphoma using radiolabeled chimeric antibodies may lead to better therapeutic responses than cold anti-CD20 antibodies. This study aimed to assess the biodistribution and present reasonable estimates of normal organ doses, including red marrow using Lu-DOTA-rituximab. Patients with relapsed/refractory CD20+ B-cell non-Hodgkin's lymphoma were recruited into this prospective study. In-house labeling of Lu-DOTA-rituximab was performed and administered after quality assurance. Rituximab (375 mg/m), followed by 50 mCi (1850 MBq) of Lu-DOTA-rituximab was administered as a slow intravenous infusion and emission images were acquired. Regions of interest were drawn for kidney, liver, heart, bladder, spleen, and tumor lesions on both anterior and posterior images. Internal dose estimation was performed using OLINDA v1.0 software. The mean age of the 10 patients (eight men and two women) was 52±13 years. The uptake of radiolabeled antibody was visualized within 30 min of administration in the liver, kidneys, heart, spleen, and bladder. The coefficient of determination (R) was greater than 0.95 for organs and the whole body in all patients. The effective half-life of radioimmunoconjugate was 100±28 h (42-126 h). The critical organ in our study was the red marrow. The average total body dose, effective dose, and effective dose equivalent calculated in all 10 patients were 0.13±0.02, 0.15±0.03, and 0.22±0.04 mGy/MBq, respectively. There may be considerable interindividual differences in absorbed doses of organs and generalization or extrapolation of doses in the clinical setting at present is not feasible with Lu-DOTA-rituximab in non-Hodgkin's lymphoma patients. Patient-specific dosimetry is thus recommended to eliminate the variations and reduce the possibility of dose-limiting toxicity.

Chemotherapy for advanced gastric cancer.

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Wagner, Anna Dorothea; Syn, Nicholas Lx; Moehler, Markus; Grothe, Wilfried; Yong, Wei Peng; Tai, Bee-Choo; Ho, Jingshan; Unverzagt, Susanne

2017-08-29

Gastric cancer is the fifth most common cancer worldwide. In "Western" countries, most people are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. In people with advanced disease, significant benefits from targeted therapies are currently limited to HER-2 positive disease treated with trastuzumab, in combination with chemotherapy, in first-line. In second-line, ramucirumab, alone or in combination with paclitaxel, demonstrated significant survival benefits. Thus, systemic chemotherapy remains the mainstay of treatment for advanced gastric cancer. Uncertainty remains regarding the choice of the regimen. To assess the efficacy of chemotherapy versus best supportive care (BSC), combination versus single-agent chemotherapy and different chemotherapy combinations in advanced gastric cancer. We searched the Cochrane Central Register of Controlled Trials, MEDLINE and Embase up to June 2016, reference lists of studies, and contacted pharmaceutical companies and experts to identify randomised controlled trials (RCTs). We considered only RCTs on systemic, intravenous or oral chemotherapy versus BSC, combination versus single-agent chemotherapy and different chemotherapy regimens in advanced gastric cancer. Two review authors independently identified studies and extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information. We included 64 RCTs, of which 60 RCTs (11,698 participants) provided data for the meta-analysis of overall survival. We found chemotherapy extends overall survival (OS) by approximately 6.7 months more than BSC (hazard ratio (HR) 0.3, 95% confidence intervals (CI) 0.24 to 0.55, 184 participants, three studies, moderate-quality evidence). Combination chemotherapy extends OS slightly (by an additional month) versus single-agent chemotherapy (HR 0.84, 95% CI 0.79 to 0.89, 4447 participants, 23 studies, moderate-quality evidence), which is

Targeting HSP70 and GRP78 in canine osteosarcoma cells in combination with doxorubicin chemotherapy.

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Asling, Jonathan; Morrison, Jodi; Mutsaers, Anthony J

2016-11-01

Heat shock proteins (HSPs) are molecular chaperones subdivided into several families based on their molecular weight. Due to their cytoprotective roles, these proteins may help protect cancer cells against chemotherapy-induced cell death. Investigation into the biologic activity of HSPs in a variety of cancers including primary bone tumors, such as osteosarcoma (OSA), is of great interest. Both human and canine OSA tumor samples have aberrant production of HSP70. This study assessed the response of canine OSA cells to inhibition of HSP70 and GRP78 by the ATP-mimetic VER-155008 and whether this treatment strategy could sensitize cells to doxorubicin chemotherapy. Single-agent VER-155008 treatment decreased cellular viability and clonogenic survival and increased apoptosis in canine OSA cell lines. However, combination schedules with doxorubicin after pretreatment with VER-155008 did not improve inhibition of cellular viability, apoptosis, or clonogenic survival. Treatment with VER-155008 prior to chemotherapy resulted in an upregulation of target proteins HSP70 and GRP78 in addition to the co-chaperone proteins Herp, C/EBP homologous transcription protein (CHOP), and BAG-1. The increased GRP78 was more cytoplasmic in location compared to untreated cells. Single-agent treatment also revealed a dose-dependent reduction in activated and total Akt. Based on these results, targeting GRP78 and HSP70 may have biologic activity in canine osteosarcoma. Further studies are required to determine if and how this strategy may impact the response of osteosarcoma cells to chemotherapy.

A randomized trial of combined multidrug chemotherapy and radiotherapy in advanced squamous cell carcinoma of the head and neck

International Nuclear Information System (INIS)

1986-01-01

This report concerns the design and results of a randomized prospective trial (SECOG I) in the treatment of advanced Stage III and IV head and neck cancer with radical radiotherapy combined with polychemotherapy. Synchronous administration of chemotherapy and radiotherapy was compared with sequential chemotherapy and radiotherapy and VBM (vincristine, bleomycin and methotrexate) compared with VBM plus 5-fluorouracil in a 2 x 2 standard factorial design. Two-hundred-and-seventy patients were entered and 267 were included in the analysis. Treatment did not present serious problems of toxicity. The addition of 5-fluorouracil to VBM produced a significant improvement in disease-free survival (P=0.04) though not in overall survival. Synchronous chemotherapy was similarly better than sequential chemotherapy, though not significantly so (P=0.1). A new study (SECOG II), based on this was started in February 1984, and one-third of the patients are now being allocated to treatment by radiotherapy as the sole method of treatment. (author)

Bendamustine and rituximab (BR) versus dexamethasone, rituximab, and cyclophosphamide (DRC) in patients with Waldenström macroglobulinemia.

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Paludo, Jonas; Abeykoon, Jithma P; Shreders, Amanda; Ansell, Stephen M; Kumar, Shaji; Ailawadhi, Sikander; King, Rebecca L; Koehler, Amber B; Reeder, Craig B; Buadi, Francis K; Dispenzieri, Angela; Lacy, Martha Q; Dingli, David; Witzig, Thomas E; Go, Ronald S; Gonsalves, Wilson I; Kourelis, Taxiarchis; Warsame, Rahma; Leung, Nelson; Habermann, Thomas M; Hayman, Suzanne; Lin, Yi; Kyle, Robert A; Rajkumar, S Vincent; Gertz, Morie A; Kapoor, Prashant

2018-04-03

The treatment approaches for Waldenstrom macroglobulinemia (WM) are largely based upon information from single-arm phase II trials, without comparative data. We compared the efficacy of two commonly used regimens in routine practice (bendamustine-rituximab (BR) and dexamethasone, rituximab plus cyclophosphamide (DRC)) and evaluated their activity with respect to the patients' MYD88 L265P mutation status. Of 160 consecutive patients, 60 received BR (43 with relapsed/refractory WM) and 100 received DRC (50 had relapsed/refractory WM). In the treatment-naïve setting, overall response rate (ORR) was 93% with BR versus 96% with DRC (p = 0.55). Two-year progression-free survival (PFS) with BR and DRC was 88 and 61%, respectively (p = 0.07). In salvage setting, ORR was 95% with BR versus 87% with DRC, p = 0.45; median PFS with BR was 58 versus 32 months with DRC (2-year PFS was 66 versus 53%; p = 0.08). Median disease-specific survival was not reached with BR versus 166 months with DRC (p = 0.51). The time-to-event endpoints and depth of response were independent of the MYD88 mutation status. Grade ≥ 3 adverse events of both regimens were comparable. A trend for longer PFS was observed with BR although the regimens have comparable toxicities. The activity of BR and DRC appears to be unaffected by patients' MYD88 mutation status.

Chemotherapy alone versus chemotherapy plus radiotherapy for early stage Hodgkin lymphoma

DEFF Research Database (Denmark)

Herbst, Christine; Rehan, Fareed Ahmed; Skoetz, Nicole

2011-01-01

BACKGROUND: Combined modality treatment (CMT) consisting of chemotherapy followed by localised radiotherapy is standard treatment for patients with early stage Hodgkin lymphoma (HL). However, due to long term adverse effects such as secondary malignancies, the role of radiotherapy has been...... chemotherapy regimen plus radiotherapy. SELECTION CRITERIA: Randomised controlled trials comparing chemotherapy alone with CMT in patients with early stage HL. Trials in which the chemotherapy differed between treatment arms were excluded. Trials with more than 20% of patients in advanced stage were also...... excluded. DATA COLLECTION AND ANALYSIS: Effect measures used were hazard ratios (HR) for tumour control and OS as well as relative risks for response rates. Two review authors independently extracted data and assessed quality of trials. We contacted study authors to obtain missing information. Since none...

Efficacy and Safety of Prolonged Rituximab Treatment in Patients with Systemic Juvenile Idiopathic Arthritis

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E. I. Alexeeva

2013-01-01

Full Text Available Aim: to assess efficacy and safety of rituximab treatment in children with systemic juvenile idiopathic arthritis under prolonged follow-up. Patients and methods: results of treatment of 60 children (33 girls and 27 boys with systemic variant of juvenile idiopathic arthritis being followed-up in rheumatology department of the Federal State Institution «Scientific Centre of Children Health» of RAMS (FSI «SCCH» RAMS were analyzed. The mean age of children was 8,7 years. The mean duration of disease course at the moment of first rituximab administration was 5,3 years. At the beginning of rituximab therapy all children had active articular syndrome, severe systemic manifestations and significantly increased laboratory markers of activity. As the signs of improvement the authors used pediatric criteria of the American College of Rheumatology. The treatment was approved by the local ethic committee of the FSI «SCCH» RAMS; the patients’ representatives and patients older than 14 years old had signed informed agreement. Results: remission was induced in 26 of 60 (43% patients: in 9 of them after the 1st course of treatment, in 8 — after the 2nd, in 6 — after the 3d and in 3 — after the 4th. The maximal duration of remission was 5 years 4 months, minimal — 6 months. Other genetically engineered drugs were administered to 34 (57% of the patients: due to the primary inefficiency in 15, secondary inefficiency — in 10; due to partial inefficiency — in 9 children. The drug was well-tolerated in most of the patients. Undesirable effects were represented by transfusional reactions to the rituximab infusion, infections with different severity and granulocytopenia. Conclusions: rituximab has high efficiency in patients with severe systemic variant of juvenile idiopathic arthritis. The drug induced remission in patients who had been considered almost incurable, with low status of physical and social adaptation.

Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study.

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Dass, S; Bowman, S J; Vital, E M; Ikeda, K; Pease, C T; Hamburger, J; Richards, A; Rauz, S; Emery, P

2008-11-01

Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS. A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) >50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with >20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy. There was significant improvement from baseline in fatigue VAS in the rituximab group (p<0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group. This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.

Combination of Intensive Chemotherapy and Anticancer Vaccines in the Treatment of Human Malignancies: The Hematological Experience

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Knut Liseth

2010-01-01

Full Text Available In vitro studies have demonstrated that cancer-specific T cell cytotoxicity can be induced both ex vivo and in vivo, but this therapeutic strategy should probably be used as an integrated part of a cancer treatment regimen. Initial chemotherapy should be administered to reduce the cancer cell burden and disease-induced immune defects. This could be followed by autologous stem cell transplantation that is a safe procedure including both high-dose disease-directed chemotherapy and the possibility for ex vivo enrichment of the immunocompetent graft cells. The most intensive conventional chemotherapy and stem cell transplantation are used especially in the treatment of aggressive hematologic malignancies; both strategies induce T cell defects that may last for several months but cancer-specific T cell reactivity is maintained after both procedures. Enhancement of anticancer T cell cytotoxicity is possible but posttransplant vaccination therapy should probably be combined with optimalisation of immunoregulatory networks. Such combinatory regimens should be suitable for patients with aggressive hematological malignancies and probably also for other cancer patients.

Chemotherapy in thyroid carcinoma

International Nuclear Information System (INIS)

Samuel, A.M.; Shah, D.H.

1999-01-01

Chemotherapy alone, either as a single drug or a combination of drugs with or without external radiation (ER) is useful for treatment of locally advanced disease and non iodine concentrating metastasis in differentiated thyroid cancers (DTC). The reported response is not encouraging, but the absence of better alternatives leave no choice for the treatment of such cases. However, for treatment of anaplastic thyroid cancers (ANC), chemotherapy (CT) in combination with ER results in local control. In medullary thyroid cancers (MTC), the results obtained with multimodal treatment are encouraging

Outcomes of Preoperative Chemoradiotherapy and Combined Chemotherapy with Radiotherapy Without Surgery for Locally Advanced Rectal Cancer.

Science.gov (United States)

Supaadirek, Chunsri; Pesee, Montien; Thamronganantasakul, Komsan; Thalangsri, Pimsiree; Krusun, Srichai; Supakalin, Narudom

2016-01-01

To evaluate the treatment outcomes of patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT) or combined chemotherapy together with radiotherapy (CMTRT) without surgery. A total of 84 patients with locally advanced rectal adenocarcinoma (stage II or III) between January 1st, 2003 and December 31st, 2013 were enrolled, 48 treated with preoperative CCRT (Gr.I) and 36 with combined chemotherapy and radiotherapy (CMTRT) without surgery (Gr.II). The chemotherapeutic agents used concurrent with radiotherapy were either 5fluorouracil short infusion plus leucovorin and/or capecitabine or 5fluorouracil infusion alone. All patients received pelvic irradiation. There were 5 patients (10.4%) with a complete pathological response. The 3 yearoverall survival rates were 83.2% in Gr.I and 24.8 % in Gr.II (prectal cancer demonstrated that in preoperative CCRT a sphincter sparing procedure can be performed. The results of treatment with preoperative CCRT for locally advanced rectal cancer showed comparable rates of overall survival and sphincter sparing procedures as compared to previous studies.

ROLE OF ADJUVANT INTRAVESICAL CHEMOTHERAPY IN THE COMBINED ORGAN-SPARING TREATMENT OF NON-MUSCLE-INVASIVE BLADDER CANCER

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A. Yu. Zubko

2014-01-01

Full Text Available Objective: to enhance the efficiency of combined treatment for non-muscle-invasive bladder cancer ((NMIBC and to assess the results of its treatment using transurethral resection (TUR as monotherapy and in combination with intravesical adjuvant chemotherapy (CT.Subjects and methods. The results of treatment were analyzed in 59 patients with NMIBC. Twenty-two patients underwent TUR in Group 1; TUR and single intravesical injection of drugs were performed in 19 patients in Group 2; 18 patients had TUR and long-term intravesical CT.Results and discussion. The recurrence rates were 59.1, 57.9, and 38.89 % in Groups 1, 2, and 3, respectively. Intravesical CT was found to appreciably affect the prevention of recurrence in the area of resection. The rate of this recurrence was 31.81, 26.32, and 5.56 % in Groups 1, 2, and 3, respectively. Conclusion. Adjuvant intravesical chemotherapy CT is an effective method to prevent recurrent bladder cancer.

Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models.

Science.gov (United States)

Herter, Sylvia; Herting, Frank; Mundigl, Olaf; Waldhauer, Inja; Weinzierl, Tina; Fauti, Tanja; Muth, Gunter; Ziegler-Landesberger, Doris; Van Puijenbroek, Erwin; Lang, Sabine; Duong, Minh Ngoc; Reslan, Lina; Gerdes, Christian A; Friess, Thomas; Baer, Ute; Burtscher, Helmut; Weidner, Michael; Dumontet, Charles; Umana, Pablo; Niederfellner, Gerhard; Bacac, Marina; Klein, Christian

2013-10-01

We report the first preclinical in vitro and in vivo comparison of GA101 (obinutuzumab), a novel glycoengineered type II CD20 monoclonal antibody, with rituximab and ofatumumab, the two currently approved type I CD20 antibodies. The three antibodies were compared in assays measuring direct cell death (AnnexinV/PI staining and time-lapse microscopy), complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and internalization. The models used for the comparison of their activity in vivo were SU-DHL4 and RL xenografts. GA101 was found to be superior to rituximab and ofatumumab in the induction of direct cell death (independent of mechanical manipulation required for cell aggregate disruption formed by antibody treatment), whereas it was 10 to 1,000 times less potent in mediating CDC. GA101 showed superior activity to rituximab and ofatumumab in ADCC and whole-blood B-cell depletion assays, and was comparable with these two in ADCP. GA101 also showed slower internalization rate upon binding to CD20 than rituximab and ofatumumab. In vivo, GA101 induced a strong antitumor effect, including complete tumor remission in the SU-DHL4 model and overall superior efficacy compared with both rituximab and ofatumumab. When rituximab-pretreated animals were used, second-line treatment with GA101 was still able to control tumor progression, whereas tumors escaped rituximab treatment. Taken together, the preclinical data show that the glyoengineered type II CD20 antibody GA101 is differentiated from the two approved type I CD20 antibodies rituximab and ofatumumab by its overall preclinical activity, further supporting its clinical investigation. ©2013 AACR.

EFFICACY OF RECURRENT RITUXIMAB TREATMENT IN PATIENT WITH SEVERE REFRACTORY SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS

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E.I. Alexeeva

2011-01-01

Full Text Available The article contains clinical case description of a severe systemic juvenile rheumatoid arthritis, that was refractory to classic immunosuppressant therapy. The disease was characterized by such extraarticular manifestations as fever, lymphadenopathy,  hepatosplenomegaly, polyserositis, generalized joint involvement and high activity in lab tests. As a result of severe clinical course of the disease, patients develop bilateral aseptic bone necrosis in coxofemoral joints and coxarthrosis. Against the background of glucocorticosteroid treatment the patient has developed hormone-dependency and hormone resistance. Inclusion into the treatment of anti-CD20 monoclonal antibodies (rituximab has stopped systemic manifestations of the disease, inflammation in the joints, normalized lab activity rates. The positive therapeutic effect allowed to perform surgery due to bilateral coxarthrosis. These results show that rituximab is highly effective in children with systemic juvenile rheumatoid arthritis, that is resistant to classic immunosupressants and glucocorticoides. Key words: children, systemic juvenile rheumatoid arthritis, rituximab, recurrent treatment, prosthetics, hip joint. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (5: 157–163.

Randomised study of sequential versus combination chemotherapy with capecitabine, irinotecan and oxaliplatin in advanced colorectal cancer, an interim safety analysis. A Dutch Colorectal Cancer Group (DCCG) phase III study.

NARCIS (Netherlands)

Koopman, M.; Antonini, N.; Douma, J.; Wals, J.; Honkoop, A.H.; Erdkamp, F.L.; Jong, R.S. de; Rodenburg, C.J.; Vreugdenhil, G.R.; Akkermans-Vogelaar, J.M.; Punt, C.J.A.

2006-01-01

BACKGROUND: Results on overall survival in randomised studies of mono- versus combination chemotherapy in advanced colorectal cancer patients may have been biased by an imbalance in salvage treatments. This is the first randomised study that evaluates sequential versus combination chemotherapy with

Randomised study of sequential versus combination chemotherapy with capecitabine, irinotecan and oxaliplatin in advanced colorectal cancer, an interim safety analysis. A Dutch Colorectal Cancer Group (DCCG) phase III study

NARCIS (Netherlands)

Koopman, M.; Antonini, N. F.; Douma, J.; Wals, J.; Honkoop, A. H.; Erdkamp, F. L. G.; de Jong, R. S.; Rodenburg, C. J.; Vreugdenhil, G.; Akkermans-Vogelaar, J. M.; Punt, C. J. A.

2006-01-01

Results on overall survival in randomised studies of mono- versus combination chemotherapy in advanced colorectal cancer patients may have been biased by an imbalance in salvage treatments. This is the first randomised study that evaluates sequential versus combination chemotherapy with a

The effect of resveratrol in combination with irradiation and chemotherapy. Study using Merkel cell carcinoma cell lines

International Nuclear Information System (INIS)

Heiduschka, G.; Lill, C.; Brunner, M.; Thurnher, D.; Seemann, R.; Schmid, R.; Houben, R.; Bigenzahn, J.

2014-01-01

Merkel cell carcinoma (MCC) is a rare, but highly malignant tumor of the skin. In case of systemic disease, possible therapeutic options include irradiation or chemotherapy. The aim of this study was to evaluate whether the flavonoid resveratrol enhances the effect of radiotherapy or chemotherapy in MCC cell lines. The two MCC cell lines MCC13 and MCC26 were treated with increasing doses of resveratrol. Combination experiments were conducted with cisplatin and etoposide. Colony forming assays were performed after sequential irradiation with 1, 2, 3, 4, 6, and 8 Gy and apoptosis was assessed with flow cytometry. Expression of cancer drug targets was analyzed by real-time PCR array. Resveratrol is cytotoxic in MCC cell lines. Cell growth is inhibited by induction of apoptosis. The combination with cisplatin and etoposide resulted in a partially synergistic inhibition of cell proliferation. Resveratrol and irradiation led to a synergistic reduction in colony formation compared to irradiation alone. Evaluation of gene expression did not show significant difference between the cell lines. Due to its radiosensitizing effect, resveratrol seems to be a promising agent in combination with radiation therapy. The amount of chemosensitizing depends on the cell lines tested. (orig.) [de

High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors.

Science.gov (United States)

Spugnini, Enrico P; Buglioni, Sabrina; Carocci, Francesca; Francesco, Menicagli; Vincenzi, Bruno; Fanciulli, Maurizio; Fais, Stefano

2014-08-21

The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. A very efficient mechanism of tumor resistance to drugs is the proton pumps-mediated acidification of tumor microenvironment. Metronomic chemotherapy has shown efficacy in adjuvant fashion as well as in the treatment of pets with advanced disease. Moreover, we have shown in veterinary clinical settings that pre-treatment with proton-pumps inhibitors (PPI) increases tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer have been recruited to be treated by a combination of metronomic chemotherapy and high dose PPIs and their responses have been matched to those of a historical control of ten patients treated with metronomic chemotherapy alone. Single arm, non randomized phase II open study, with historical control group, evaluating safety and efficacy of the combination of metronomic chemotherapy and alkalization. Twenty-four companion animals (22 dogs and 2 cats) were treated adding to their metronomic chemotherapy protocol the pump inhibitor lansoprazole at high dose, and a water alkalizer. Their responses have been evaluated by clinical and instrumental evaluation and matched to those of the control group. The protocol was overall well tolerated, with only two dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response, in the alkalized cohort, 18 out of 24 had partial or complete responses (75%), two patients had a stable disease and the remaining patients experienced no response or progressive disease. On the other hand, only one patient in the control group experienced a complete response (10%) and three other experienced short lived responses. Median time to terminal event was 34 weeks for the experimental group versus 2 weeks in the controls (p= 0.042). Patient alkalization has shown to be well tolerated and to increase tumor response

Intra-arterial chemotherapy for locally advanced bladder cancer

International Nuclear Information System (INIS)

Aota, Yasuhiro; Yoshida, Kazuhiko

1999-01-01

A total of 83 patients with locally advanced bladder cancer (T1, n=5; T2, n=28; T3a, n=21; T3b, n=21; T4, n=8) were treated with intra-arterial (i.a.) cisplatin and adriamycin (or epirubicin) chemotherapy. In 51 of the 83 cases, we combined this treatment with radiotherapy. The pathological complete response (CR) rate was 68% for all patients, 84% for i.a. chemotherapy combined with radiotherapy and only 41% for i.a. chemotherapy. The 5-year survival rate was 57% for all patients, 71% for i.a. chemotherapy combined with radiotherapy and only 44% for i.a. chemotherapy. The 5-year survival as a function of the clinical stage was 82% for T1+T2, 66% for T3a, 28% for T3b, 25% for T4 (T1+T2 vs. T3b: p<0.001, T1+T2 vs. T4: p<0.0001, T3a vs. T3b: p<0.0263, T3a vs. T4: p<0.0214, T3b vs. T4: p<0.029). In 46% of all patients, we succeeded in preserving the bladder; especially noteworthy, is that in 65% of the patients undergoing i.a. chemotherapy combined with radiotherapy, we succeeded in preserving the bladder. These results demonstrate that i.a. chemotherapy combined with radiotherapy is a useful method for locally advanced bladder cancer which may make preservation of the bladder function feasible. (author)

Effect of Xiao Chaihu Tang combined with intravenous chemotherapy on tumor markers and immune function in patients with advanced breast cancer

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Jian-Ping Zhong

2017-05-01

Full Text Available Objective: To study the effect of Xiao Chaihu Tang combined with intravenous chemotherapy on tumor markers and immune function in patients with advanced breast cancer. Methods: 76 patients with advanced breast cancer treated in our hospital between May 2012 and November 2015 were collected and divided into the combined treatment group (n=34 who accepted Xiao Chaihu Tang combined with intravenous chemotherapy and the control group (n=42 who accepted intravenous chemotherapy alone according to different treatment, and the treatment cycle was 3 months for both groups. Before treatment and 3 months after treatment, ELISA method was used to detect serum levels of broad-spectrum tumor markers and breast cancerspecific tumor markers; flow cytometer was used to detect cellular immune function index levels, and turbidimetric immunoassay was used to detect humoral immune function index levels in peripheral blood. Results: Before treatment, differences in serum tumor marker levels as well as cellular immunity and humoral immunity index levels in peripheral blood were not statistically significant between two groups of patients (P>0.05; after 3 months of treatment, broad-spectrum tumor markers carcinoembryonic antigen (CEA, carbohydrate antigen 153 (CA153 and carbohydrate antigen 125 (CA125 levels in serum of combined treatment group were lower than those of control group, and breast cancer-specific tumor markers insulin-like growth factor-1 (IGF-1, midkine (MK, soluble E-cadherin (sEC and thymidine kinase 1 (TK1 levels were lower than those of control group (P<0.05; CD3+ and CD4+ T lymphocyte levels as well as CD4+/CD8+ ratio in peripheral blood of combined treatment group were higher than those of control group while CD8+ T lymphocyte level was lower than that of control group, and immunoglobulin G (IgG, immunoglobulin A (IgA and immunoglobulin M (IgM levels in peripheral blood were higher than those of control group (P<0.05. Conclusions: Xiao Chaihu Tang

Treatment of recurrent head and neck cancers: results of two radio chemotherapy combinations

Energy Technology Data Exchange (ETDEWEB)

Khanfir, K.; Wibault, P.; Koscielny, S.; Crevoisier, R. de; Biron, B.; Domenge, C.; Lusinchi, A.; Luboinski, B.; Eschewege, F.; Bourhis, J. [Institut Gustave Roussy, 94 - Villejuif (France)

2002-11-01

Despite much more intense treatment in the 3 - D group, the acute toxicity was not significantly different between the two groups. A complete tumor regression was observed in 41 % of the patients in the 2- D group and 58 % in the 3- D group. however, given the short follow-up and the relatively limited number of patients in the 3 - D group, conclusions regarding tumor response need further investigations. The use of 3 - D conformal radiotherapy allowed to increase the dose intensity of re irradiation combined with chemotherapy, without increasing deleterious effect. (N.C.)

The effect of hyperthermia in the preoperative combined treatment of radiation, hyperthermia and chemotherapy for rectal carcinoma

Energy Technology Data Exchange (ETDEWEB)

Konishi, Fumio; Furuta, Kazuhiro; Saito, Yukio; Kataoka, Takashi; Kashiwagi, Hiroshi; Okada, Masaki; Kanazawa, Kyotaro; Sugahara, Tadashi; Shinohara, Naohiro (Jichi Medical School, Minamikawachi, Tochigi (Japan))

1994-03-01

To investigate the effectiveness of hyperthermia in the preoperative combined treatment of radiation, chemotherapy and hyperthermia for rectal carcinoma, two groups were compared. Group A consisted of 18 patients in whom hyperthermia, radiation and chemotherapy were performed. Group B consisted of 18 patients in whom only chemotherapy and radiation were performed. The total dose of radiation in both of the two groups was 40.5 Gy, and a radiation field covering the whole pelvis was used. Hyperthermia was performed using 8 MHz radiofrequency waves (Thermotron RF8, Yamamoto Vinyter, Japan), and tumors were heated at about 42 degrees C for 50 minutes. Hyperthermia was repeated five times during the preoperative treatment. Chemotherapy was performed by giving 5-fluorouracil suppositories to a total dose of 3400 mg. Mean tumor reduction rates on barium enema were 31.8% in group A and 18.2% in group B. The difference was statistically significant. The result of the histological assessment of tumor necrosis showed that there was a significantly higher degree of necrosis in group A than in group B. These results showed that the addition of hyperthermia enhanced tumor necrosis. It was concluded that the addition of hyperthermia would be an effective preoperative treatment of rectal carcinoma. (author).

The effect of hyperthermia in the preoperative combined treatment of radiation, hyperthermia and chemotherapy for rectal carcinoma

International Nuclear Information System (INIS)

Konishi, Fumio; Furuta, Kazuhiro; Saito, Yukio; Kataoka, Takashi; Kashiwagi, Hiroshi; Okada, Masaki; Kanazawa, Kyotaro; Sugahara, Tadashi; Shinohara, Naohiro

1994-01-01

To investigate the effectiveness of hyperthermia in the preoperative combined treatment of radiation, chemotherapy and hyperthermia for rectal carcinoma, two groups were compared. Group A consisted of 18 patients in whom hyperthermia, radiation and chemotherapy were performed. Group B consisted of 18 patients in whom only chemotherapy and radiation were performed. The total dose of radiation in both of the two groups was 40.5 Gy, and a radiation field covering the whole pelvis was used. Hyperthermia was performed using 8 MHz radiofrequency waves (Thermotron RF8, Yamamoto Vinyter, Japan), and tumors were heated at about 42 degrees C for 50 minutes. Hyperthermia was repeated five times during the preoperative treatment. Chemotherapy was performed by giving 5-fluorouracil suppositories to a total dose of 3400 mg. Mean tumor reduction rates on barium enema were 31.8% in group A and 18.2% in group B. The difference was statistically significant. The result of the histological assessment of tumor necrosis showed that there was a significantly higher degree of necrosis in group A than in group B. These results showed that the addition of hyperthermia enhanced tumor necrosis. It was concluded that the addition of hyperthermia would be an effective preoperative treatment of rectal carcinoma. (author)

A Phase I Study of Pulse High-Dose Vorinostat (V) plus Rituximab (R), Ifosphamide, Carboplatin, and Etoposide (ICE) in Patients with Relapsed Lymphoma

Science.gov (United States)

Budde, Lihua E.; Zhang, Michelle M.; Shustov, Andrei R.; Pagel, John M.; Gooley, Ted A.; Oliveira, George R.; Chen, Tara L.; Knudsen, Nancy L.; Roden, Jennifer E.; Kammerer, Britt E.; Frayo, Shani L.; Warr, Thomas A.; Boyd, Thomas E.; Press, Oliver W.; Gopal, Ajay K.

2013-01-01

SUMMARY Given the poor outcomes of relapsed aggressive lymphomas and preclinical data suggesting that ≥2.5 μM concentrations of vorinostat synergize with both etoposide and platinums, we hypothesized that pulse high-dose vorinostat could safely augment the anti-tumour activity of (R)ICE [(rituximab), ifosphamide, carboplatin, etoposide] chemotherapy. We conducted a phase I dose escalation study using a schedule with oral vorinostat ranging from 400 mg/d to 700 mg bid for 5 days in combination with the standard (R)ICE regimen (days 3, 4 and 5). Twenty-nine patients (median age 56 years, median 2 prior therapies, 14 chemoresistant [of 27 evaluable], 2 prior transplants) were enrolled and treated. The maximally tolerated vorinostat dose was defined as 500 mg twice daily × 5 days. Common dose limiting toxicities included infection (n=2), hypokalaemia (n=2), and transaminitis (n=2). Grade 3 related gastrointestinal toxicity was seen in 9 patients. The median vorinostat concentration on day 3 was 4.5 μM (range 4.2–6.0 μM) and in vitro data confirmed the augmented antitumour and histone acetylation activity at these levels. Responses were observed in 19 of 27 evaluable patients (70%) including 8 complete response/unconfirmed complete response. High-dose vorinostat can be delivered safely with (R)ICE, achieves potentially synergistic drug levels, and warrants further study, although adequate gastrointestinal prophylaxis is warranted. PMID:23356514

Treatment results and complications in clinical combinations of radiation and chemotherapy in the treatment of localized cancer in the head and neck

International Nuclear Information System (INIS)

Masaki, Norie; Shigematsu, Yasushi

1981-01-01

By using chemotherapy combined with radiotherapy, significant improvements were achieved in treatment results of localized non-Hodgkin's lymphoma, intraoral cancer, and carcinoma of the maxillary sinus. Administering chemotherapy with radiation was given sumultaneously in the patients with intraoral cancer (BLM iv) and with carcinoma of the maxillary sinus (5-FU ia). In the patients with non-Hodgkin's lymphoma, chemotherapy (1 or 2 cycles of COPP) was administered and followed by radiotherapy. If radiation dose were reduced by about 50% in the intraoral cancer, 20% in carcinoma of the maxillary sinus, and 10% in non-Hodgkin's lymphoma, acute and/or chronic complications were within tolerable limits in this series of observations, although toxicity was dose-related for both chemotherapy and radiotherapy. (author)

Prognostic value of hemoglobin concentrations in patients with advanced head and neck cancer treated with combined radio-chemotherapy and surgery

International Nuclear Information System (INIS)

Wagner, W.; Hermann, R.; Koch, O.; Hartlapp, J.; Krech, R.

2000-01-01

Purpose: Hemoglobin levels are currently the focus of interest as prognostic factors in patients with head and neck cancer. Most published clinical trials have confirmed hemoglobin to process a significant influence on survival in patients treated with radiotherapy. In our study we have investigated the prognostic value of hemoglobin in a combined modality schedule. Patients and Methods: Forty-three patients with advanced head and neck tumors were treated with combined radiochemotherapy. The therapy comprised 2 courses of induction chemotherapy with ifosfamide (1,500 mg/m 2 , day 1 to 5) and cisplatin (60 mg/m 2 , day 5) followed by hyperfractionated accelerated radiotherapy with a total dose of only 30 Gy. Surgery involved tumor resection and neck dissection. Results: The 1-year overall survival rate and the 2-year survival rate were 79% and 56%, respectively. The 1- and 2-year recurrence-free survival rates were 68% and 49%, respectively. Prognostic factors with an impact on survival were seen in tumor size (T3 vs T4, p=0.0088), response to radio-chemotherapy at the primary site (no vital tumor rest vs vital tumor rest, p=0.045), response to lymph node radio-chemotherapy (no vital tumor cells vs vital tumor cells, p=0.013) and level of hemoglobin after radio-chemotherapy (Hb≥11.5 g/dl vs [de

IMPACT OF PRE-TRANSPLANT RITUXIMAB ON SURVIVAL AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA

Science.gov (United States)

Fenske, Timothy S.; Hari, Parameswaran N.; Carreras, Jeanette; Zhang, Mei-Jie; Kamble, Rammurti T.; Bolwell, Brian J.; Cairo, Mitchell S.; Champlin, Richard E.; Chen, Yi-Bin; Freytes, César O.; Gale, Robert Peter; Hale, Gregory A.; Ilhan, Osman; Khoury, H. Jean; Lister, John; Maharaj, Dipnarine; Marks, David I.; Munker, Reinhold; Pecora, Andrew L.; Rowlings, Philip A.; Shea, Thomas C.; Stiff, Patrick; Wiernik, Peter H.; Winter, Jane N.; Rizzo, J. Douglas; van Besien, Koen; Lazarus, Hillard M.; Vose, Julie M.

2010-01-01

Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens for diffuse large B-cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, many patients develop refractory or recurrent DLBCL and then receive autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes following AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n=176, “+R” group) or was not (n=818, “ −R” group) administered with front-line or salvage therapy prior to AuHCT. The +R group had superior progression-free survival (50% versus 38%, p=0.008) and overall survival (57% versus 45%, p=0.006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Non-relapse mortality (NRM) did not differ significantly between the +R and −R groups. In multivariate analysis, the +R group had improved progression-free survival (relative risk of relapse/progression or death 0.64, p<0.001) and improved overall survival (relative risk of death of 0.74, p=0.039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival following AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM. PMID:19822306

A multi-centre retrospective study of rituximab use in the treatment of relapsed or resistant warm autoimmune haemolytic anaemia.

LENUS (Irish Health Repository)

Maung, Su W

2013-10-01

This retrospective analysis assessed the response, safety and duration of response to standard dose rituximab 375 mg\\/m(2) weekly for four weeks as therapy for patients with primary or secondary warm autoimmune haemolytic anaemia (WAIHA), who had failed initial treatment. Thirty-four patients received rituximab for WAIHA in seven centres in the Republic of Ireland. The overall response rate was 70·6% (24\\/34) with 26·5% (9\\/34) achieving a complete response (CR). The time to response was 1 month post-initiation of rituximab in 87·5% (21\\/24) and 3 months in 12·5% (3\\/24) of patients. The median duration of follow-up was 36 months (range 6-90 months). Of the patients who responded, 50% (12\\/24) relapsed during follow up with a median time to next treatment of 16·5 months (range 6-60 months). Three patients were re-treated with rituximab 375 mg\\/m2 weekly for four weeks at relapse and responded. There was a single episode of neutropenic sepsis. Rituximab is an effective and safe treatment for WAIHA but a significant number of patients will relapse in the first two years post treatment. Re-treatment was effective in a small number of patients, suggesting that intermittent pulse treatment or maintenance treatment may improve long-term response.

B-lymphocyte reconstitution after repeated rituximab treatment in a child with steroid-dependent autoimmune hemolytic anemia

Directory of Open Access Journals (Sweden)

Annelieke A.A. van der Linde

2011-12-01

Full Text Available We report the detailed long-term reconstitution of B-lymphocyte subpopulations, immunoglobulins, and specific antibody production after two courses of rituximab in a young, previously healthy girl with steroid-dependent autoimmune hemolytic anemia. B-lymphocyte subpopulations were surprisingly normal directly after reconstitution. However, there was a slower reconstitution after the second rituximab course, especially of non-switched and switched memory B-lymphocytes, and a temporary decline in IgM below age-matched reference values.

Combined CT-guided radiofrequency ablation with systemic chemotherapy improves the survival for nasopharyngeal carcinoma with oligometastasis in liver: Propensity score matching analysis.

Science.gov (United States)

Li, Wang; Bai, Yutong; Wu, Ming; Shen, Lujun; Shi, Feng; Sun, Xuqi; Lin, Caijin; Chang, Boyang; Pan, Changchuan; Li, Zhiwen; Wu, Peihong

2017-08-08

The aim of this study was to retrospectively compare the treatment efficacy of systemic chemotherapy combined with sequential CT-guided radiofrequency ablation (Chemo-RFA) to chemotherapy alone (Chemo-only) in the management of nasopharyngeal carcinoma (NPC) with liver metastasis. Between 2003 and 2011, 328 NPC patients diagnosed with liver metastasis at Sun Yat-sen University Cancer Center were enrolled. One-to-one matched pairs between Chemo-RFA group with the Chemo-only group were generated using propensity score matching. The associations of treatment modality with overall survival (OS) and progression-free survival (PFS) were determined by Cox regression. Of the patients enrolled, 37 patients (11.8 %) received combined treatment, 291 (82.2) received chemotherapy alone. The patients in Chemo-RFA group were more frequently classified as lower number (≤3) of liver metastatic lesions (Poligometastasis in liver, and should be considered if the ablation is technically feasible.

The protein kinase C (PKC) inhibitors combined with chemotherapy in the treatment of advanced non-small cell lung cancer: meta-analysis of randomized controlled trials.

Science.gov (United States)

Zhang, L L; Cao, F F; Wang, Y; Meng, F L; Zhang, Y; Zhong, D S; Zhou, Q H

2015-05-01

The application of newer signaling pathway-targeted agents has become an important addition to chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). In this study, we evaluated the efficacy and toxicities of PKC inhibitors combined with chemotherapy versus chemotherapy alone for patients with advanced NSCLC systematically. Literature retrieval, trials selection and assessment, data collection, and statistic analysis were performed according to the Cochrane Handbook 5.1.0. The outcome measures were tumor response rate, disease control rate, progression-free survival (PFS), overall survival (OS), and adverse effects. Five randomized controlled trials, comprising totally 1,005 patients, were included in this study. Meta-analysis showed significantly decreased response rate (RR 0.79; 95 % CI 0.64-0.99) and disease control rate (RR 0.90; 95 % CI 0.82-0.99) in PKC inhibitors-chemotherapy groups versus chemotherapy groups. There was no significant difference between the two treatment groups regarding progression-free survival (PFS, HR 1.05; 95 % CI 0.91-1.22) and overall survival (OS, HR 1.00; 95 % CI 0.86-1.16). The risk of grade 3/4 neutropenia, leucopenia, and thrombosis/embolism increased significantly in PKC inhibitors combination groups as compared with chemotherapy alone groups. The use of PKC inhibitors in addition to chemotherapy was not a valid alternative for patients with advanced NSCLC.

Combination of EGFR-TKIs and chemotherapy as first-line therapy for advanced NSCLC: a meta-analysis.

Science.gov (United States)

OuYang, Pu-Yun; Su, Zhen; Mao, Yan-Ping; Deng, Wuguo; Xie, Fang-Yun

2013-01-01

The impact of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. Therefore, randomized trials that compared this combined regimen with chemotherapy or EGFR-TKIs monotherapy were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of the combined regimen in the entire unselected population and selected patients by EGFR-mutation status and smoking history were calculated. Eight trials eventually entered into this meta-analysis, including 4585 patients. Overall, the combined regimen significantly delayed disease progression (HR = 0.81, 95% CI 0.69-0.95, P = 0.01); subgroup analysis showed significantly higher progression free survival advantages in Asian patients (Pchemotherapy (P = 0.02). In selected patients by EGFR-mutation, both mutation positive (HR = 0.48, 95% CI 0.28-0.83, P = 0.009) and negative (HR = 0.84, 95% CI 0.72-0.98, P = 0.02) patients gained progression free survival benefit from the combined regimen, albeit the magnitude of benefit was marginally larger in mutation positive patients (P = 0.05). In selected patients by smoking history, never/light smokers achieved a great progression free survival benefit from the combined regimen (HR = 0.51, 95% CI 0.35-0.74, P = 0.0004). Unfortunately, the combined regimen had no significant impact on overall survival, irrespective of ethnicity, dose schedules or EGFR-mutation status. Severe anorexia (RR = 2.01, 95% CI 1.11-3.63; P = 0.02) and diarrhea (RR = 2.70, 95% CI 1.94-3.76; Pchemotherapy deserved to be considered in the future, although it is not approved for advanced NSCLC at the moment.

Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab.

Science.gov (United States)

Aggarwal, Rohit; Oddis, Chester V; Goudeau, Danielle; Koontz, Diane; Qi, Zengbiao; Reed, Ann M; Ascherman, Dana P; Levesque, Marc C

2016-06-01

To determine the longitudinal trends in serum levels of four myositis-associated autoantibodies: anti-Jo-1, -transcription intermediary factor 1 γ (TIF1-γ), -signal recognition particle (SRP) and -Mi-2, after B cell depletion with rituximab, and to determine the longitudinal association of these autoantibody levels with disease activity as measured by myositis core-set measures (CSMs). Treatment-resistant adult and pediatric myositis subjects (n = 200) received rituximab in the 44-week Rituximab in Myositis Trial. CSMs [muscle enzymes, manual muscle testing (MMT), physician and patient global disease activity, HAQ, and extramuscular disease activity] were evaluated monthly and anti-Jo-1 (n = 28), -TIF1-γ (n = 23), -SRP (n = 25) and -Mi-2 (n = 26) serum levels were measured using validated quantitative ELISAs. Temporal trends and the longitudinal relationship between myositis-associated autoantibodies levels and CSM were estimated using linear mixed models. Following rituximab, anti-Jo-1 levels decreased over time (P myositis subjects decreased after B cell depletion and were correlated with changes in disease activity, whereas anti-SRP levels were only associated with longitudinal muscle enzyme levels. The strong association of anti-Jo-1 levels with clinical outcomes suggests that anti-Jo-1 autoantibodies may be a good biomarker for disease activity. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Combined radiotherapy and chemotherapy for high-grade brain tumours

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Barazzuol, Lara

Glioblastoma (GBM) is the most common primary brain tumour in adults and among the most aggressive of all tumours. For several decades, the standard care of GBM was surgical resection followed by radiotherapy alone. In 2005, a landmark phase III clinical trial coordinated by the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC) demonstrated the benefit of radiotherapy with concomitant and adjuvant temozolomide (TMZ) chemotherapy. With TMZ, the median life expectancy in optimally managed patients is still only 12-14 months, with only 25% surviving 24 months. There is an urgent need for new therapies in particular in those patients whose tumour has an unmethylated methylguanine methyltransferase gene (MGMT) promoter, which is a predictive factor of benefit from TMZ. In this dissertation, the nature of the interaction between TMZ and radiation is investigated using both a mathematical model, based on in vivo population statistics of survival, and in vitro experimentation on a panel of human GBM cell lines. The results show that TMZ has an additive effect in vitro and that the population-based model may be insufficient in predicting TMZ response. The combination of TMZ with particle therapy is also investigated. Very little preclinical data exists on the effects of charged particles on GBM cell lines as well as on the concomitant application of chemotherapy. In this study, human GBM cells are exposed to 3 MeV protons and 6 MeV alpha particles in concomitance with TMZ. The results suggest that the radiation quality does not affect the nature of the interaction between TMZ and radiation, showing reproducible additive cytotoxicity. Since TMZ and radiation cause DNA damage in cancer cells, there has been increased attention to the use of poly(ADP-ribose) polymerase (PARP) inhibitors. PARP is a family of enzymes that play a key role in the repair of DNA breaks. In this study, a novel PARP inhibitor, ABT-888

Rituximab therapy in steroid-resistant severe hypothyroid Grave′s ophthalmopathy

Directory of Open Access Journals (Sweden)

Aditi Pandit

2013-01-01

Full Text Available Association of Grave′s ophthalmopathy with hyperthyroidism is well known, and it has also been reported in euthyroid or hypothyroid autoimmune thyroiditis, which rarely requires treatment. Here, we report a case of bilaterally symmetrical severe corticosteroid-resistant hypothyroid Grave′s ophthalmopathy successfully treated with rituximab.

Pilot studies of superfractionated radiotherapy and combination chemotherapy in limited oat cell carcinoma of the bronchus

International Nuclear Information System (INIS)

Hodson, D.I.; Malaker, K.; Meikle, A.L.; Levitt, M.

1984-01-01

There are sound radiobiologic and suggestive clinical rationale for superfractionating the radiotherapeutic regimens employed for the therapy of rapidly growing malignancies. Oat cell carcinoma of the bronchus is such a tumor. The authors report their experience combining aggressive systemic combination chemotherapy with supperfractionated radiotherapy for the treatment of limited oat cell carcinoma of the bronchus. Overall, patient tolerance was satisfactory and a complete remission rate of 74% was achieved. It remains to be proven, in a prospective randomized fashion, whether this approach is superior to current conventional management

A phase II study of VP-16-ifosfamide-cisplatin combination chemotherapy plus early concurrent thoracic irradiation for previously untreated limited small cell lung cancer

International Nuclear Information System (INIS)

Woo, In Sook; Park, Young Suk; Kwon, Sung Hee

2000-01-01

At present the addition of thoracic irradiation to combination chemotherapy is a standard treatment for limited staged small cell ling cancer. However, there is still controversy about the optimum timing of chest irradiation. We conducted a phase II study of etoposide (VP-16)-ifosfamide-cisplatin (VIP) combination chemotherapy plus early concurrent thoracic irradiation for the patients with previously untreated limited small cell lung cancer in order to assess if the treatment modality could improve the response rate and the toxicity. Forty-four patients with limited small cell lung cancer were treated with etoposide-ifosfamide-cisplatin and concurrent thoracic irradiation. Combination chemotherapy consisted of etoposide 100 mg/m 2 (on day 1-3), ifosfamide 1000 mg/m 2 (on days 1 and 2) and cisplatin 100 mg/m 2 (on day 1). Concurrent thoracic irradiation consisted of a total of 4000 cGy over 4 weeks starting on the first day of the first chemotherapy. All patients who showed a complete response were given prophylactic cranial irradiation for 2.5 weeks. Forty-four of the 49 patients who entered the study from May 1994 to August 1998 were evaluable. The median age was 59 years and 40 patients had a performance status of 0 or 1. The median survival time was 22.5 months. Twenty-eight patients (62%) showed a complete response and 16 (38%) a partial response. Twenty-four patients (54%) developed grade 3 or 4 neutropenia; there was a 9% RTOG score 3 or 4 esophagitis. VIP combination chemotherapy and early concurrent thoracic irradiation for patients with limited stage small cell lung cancer revealed excellent antitumor response with tolerable toxicity. (author)

Lenalidomide-bendamustine-rituximab in untreated mantle cell lymphoma > 65 years with untreated mantle cell lymphoma

DEFF Research Database (Denmark)

Albertsson-Lindblad, Alexandra; Kolstad, Arne; Laurell, Anna

2016-01-01

For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years with untr......For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years...

Treatment of small cell carcinoma of lung with combined high dose mediastinal irradiation, whole brain prophylaxis and chemotherapy

International Nuclear Information System (INIS)

Shank, B.; Natale, R.B.; Hilaris, B.S.; Wittes, R.E.

1981-01-01

Survival of patients with small cell carcinoma of lung, treated on a new combined radiotherapy-chemotherapy protocol, compares favorably with other regimens in the literature and our own previous combined approaches. Radiation, given after induction chemotherapy, consisted of whole brain prophylaxis in all 44 evaluable patients. Patients with limited disease were also treated to the primary and mediastinum to a high dose (5000 rad equivalent) using multiple fields. The new chemotherapy regimen consisted of induction with cyclophosphamide, doxorubicin, and vincristine alternated with cis-platinum and VP-16 (an epipodophyllotoxin) for two cycles, followed by consolidation with low dose cyclophosphamide and vincristine concurrent with irradiation. Patients with limited disease who achieved less than complete response, and all patients with extensive disease were not continued on maintenance chemotherapy. Out of 24 evaluable patients with limited disease, there was 73% survival at 1 year by life-table analysis, measured from treatment initiation. After induction, 16/24 of these limited disease patients were CR (complete responders): 20/24 were CR at completion of their irradiation. Out of 20 evaluable patients with extensive disease, there was 59% survival at 1 year by life-table analysis. Only 4/44 (9%) brain parenchymal relapses occurred, one at 3 months and one at 6 months after local failure and two in patients who did not become CRs, implicating a possible re-seeding mechanism. Five patients had central nervous system relapses outside of brain parenchyma (spinal epidural and leptomeningeal); in three patients this was the initial site of failure. Significant complications included leukopenia (50%) and thrombocytopenia (24%) primarily during induction, and chronic pulmonary fibrosis (25%), possibly contributing to two deaths

[Supportive care during chemotherapy for lung cancer in daily practice].

Science.gov (United States)

Müller, Veronika; Tamási, Lilla; Gálffy, Gabriella; Losonczy, György

2012-09-01

Active oncotherapy, combination chemotherapy of lung cancer is accompanied with many side effects which may impair patients' quality of life and compromise the effectiveness of chemotherapy. Most side effects of chemotherapy are preventable or treatable with optimal supportive care which enhances success in patient care and treatment. The aim of this review is to summarize the most important conditions that may be associated with combined chemotherapy of lung cancer from the practical point of view.

Nanoscaled red blood cells facilitate breast cancer treatment by combining photothermal/photodynamic therapy and chemotherapy.

Science.gov (United States)

Wan, Guoyun; Chen, Bowei; Li, Ling; Wang, Dan; Shi, Shurui; Zhang, Tao; Wang, Yue; Zhang, Lianyun; Wang, Yinsong

2018-02-01

Red blood cells (RBCs)-based vesicles have been widely used for drug delivery due to their unique advantages. Intact RBCs contain a large amount of oxyhemoglobin (oxyHb), which can assist with photodynamic therapy (PDT). Indocyanine green (ICG), a photosensitizer both for photothermal therapy (PTT) and PDT, shows potent anticancer efficacy when combined with chemotherapeutic drug doxorubicin (DOX). In this study, we prepared nanoscaled RBCs (RAs) containing oxyHb and gas-generating agent ammonium bicarbonate (ABC) for co-loading and controlled release of ICG and DOX, thus hoping to achieve synergistic effects of PTT/PDT and chemotherapy against breast cancer. Compared to free ICG, ICG and DOX co-loaded RAs (DIRAs) exhibited nearly identical PTT efficiency both in vitro and in vivo, but meanwhile their PDT efficiency was enhanced significantly. In mouse breast cancer cells, DIRAs significantly inhibited cell growth and induced cell apoptosis after laser irradiation. In breast tumor-bearing mice, intratumoral injection of DIRAs and followed by local laser irradiation almost completely ablated breast tumor and further suppressed tumor recurrence and metastasis. In conclusion, this biomimetic multifunctional nanosystem can facilitate breast cancer treatment by combining PTT/PDT and chemotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bladder cancer: The combination of chemotherapy and irradiation in the treatment of patients with muscle-invading tumors

International Nuclear Information System (INIS)

Shipley, William U.; Zietman, Anthony L.

1996-01-01

In the USA the recommended treatment for patients with muscle-invading transitional cell cancer of the bladder is usually radical cystectomy. Conservative surgery irradiation, and cisplatin-based systemic chemotherapy are, however, each effective for some patients. Although they provide the opportunity for bladder preservation, each modality, when used alone, is inferior to radical cystectomy in terms of local control and, perhaps, survival. Many recent publications have now documented the efficacy of combined modality treatment protocols employing all three of these modalities together. All employ a selective approach in which the patients only receive full-dose radiation if they have had a complete response to induction CMT. Overall survival data for T2-T3a patients are certainly as good as any reported cystectomy series of similarly clinically staged and similar aged patients. Radiation adds very significantly to the transurethral resection and systemic chemotherapy to maintain the bladder free of tumor. Substantially higher rates of pathologic confirmation of complete response are found following transurethral surgery and chemoradiation when compared with transurethral surgery and chemotherapy omitting the radiation. Overall survival is as good as cystectomy based approaches at 48-54% and over 80% of these long-term survivors keep their bladders. Following such therapies, 20-30% will subsequently develop superficial tumors. These patients may still be well treated by standard methods using transurethral resection and intravesical drugs. The concern of urologists that the conserved irradiated bladder functions poorly has also been answered by recent reports using modern radiation techniques. The instance of cystectomy for bladder shrinkage is repeatedly below 2%. Furthermore, sexual function is commonly preserved. The systemic morbidity of the chemotherapy is relatively high, but new approached using anti-emetics and GCSF now allow this to be reduced. In many

Postirradiation soft tissue sarcoma occurring in breast cancer patients: report of seven cases and results of combination chemotherapy

International Nuclear Information System (INIS)

Kuten, A.; Sapir, D.; Cohen, Y.; Haim, N.; Borovik, R.; Robinson, E.

1985-01-01

Seven cases of soft tissue sarcoma developing after primary or postoperative radiotherapy for breast carcinoma are reported. The sarcomas occurred within the irradiated volume, after a latent period of 4-26 years. These cases conform well to established criteria for the diagnosis of radiation-induced sarcoma. Chemotherapy, consisting of the four-drug combination CYVADIC (cyclophosphamide, vincristine, adriamycin, DTIC) was employed in six of the seven patients. Only two of them achieved partial remission, lasting only 2 and 3 months, respectively. The effectiveness of adriamycin-containing chemotherapy regimens in soft tissue sarcomas as well as the remote hazard of radiation-related sarcoma in primary or postoperative breast irradiation are discussed

A systematic review and meta-analysis of traditional insect Chinese medicines combined chemotherapy for non-surgical hepatocellular carcinoma therapy.

Science.gov (United States)

Shi, Zhaofeng; Song, Tiebing; Wan, Yi; Xie, Juan; Yan, Yiquan; Shi, Kekai; Du, Yongping; Shang, Lei

2017-06-28

On the background of high morbidity and mortality of hepatocellular carcinoma (HCC) and rapid development of traditional Chinese medicine (TCM), we conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to assess the clinical effectiveness and safety of traditional insect Chinese medicine and related preparation for non-surgical HCC. RCTs were searched based on standardized searching rules in mainstream medical databases from the inception up to May 2016. Ultimately, a total of 57 articles with 4,651 patients enrolled in this meta-analysis. We found that traditional insect Chinese medicine and related preparation combined chemotherapy show significantly effectiveness and safety in objective response rate (P traditional insect Chinese medicine and related preparations could be recommended as auxiliary therapy combined chemotherapy for HCC therapy.

Phase I and pharmacologic study of the combination paclitaxel and carboplatin as first-line chemotherapy in stage III and IV ovarian cancer

NARCIS (Netherlands)

Huizing, M. T.; van Warmerdam, L. J.; Rosing, H.; Schaefers, M. C.; Lai, A.; Helmerhorst, T. J.; Veenhof, C. H.; Birkhofer, M. J.; Rodenhuis, S.; Beijnen, J. H.; ten Bokkel Huinink, W. W.

1997-01-01

To determine the maximum-tolerated dose for the combination paclitaxel and carboplatin administered every 4 weeks and to gain more insight into the pharmacokinetics and pharmacodynamics of this combination in previously untreated ovarian cancer patients. Thirty-five chemotherapy-naive patients with

Rituximab Extended Schedule or Re-Treatment Trial for Low–Tumor Burden Follicular Lymphoma: Eastern Cooperative Oncology Group Protocol E4402

Science.gov (United States)

Kahl, Brad S.; Hong, Fangxin; Williams, Michael E.; Gascoyne, Randy D.; Wagner, Lynne I.; Krauss, John C.; Habermann, Thomas M.; Swinnen, Lode J.; Schuster, Stephen J.; Peterson, Christopher G.; Sborov, Mark D.; Martin, S. Eric; Weiss, Matthias; Ehmann, W. Christopher; Horning, Sandra J.

2014-01-01

Purpose In low–tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival when compared with observation. It is not known whether MR provides superior long-term disease control compared with re-treatment rituximab (RR) administered on an as-needed basis. E4402 (RESORT) was a randomized clinical trial designed to compare MR against RR. Patients and Methods Eligible patients with previously untreated low–tumor burden FL received four doses of rituximab, and responding patients were randomly assigned to either RR or MR. Patients receiving RR were eligible for re-treatment at each disease progression until treatment failure. Patients assigned to MR received a single dose of rituximab every 3 months until treatment failure. The primary end point was time to treatment failure. Secondary end points included time to first cytotoxic therapy, toxicity, and health-related quality of life (HRQOL). Results A total of 289 patients were randomly assigned to RR or MR. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years for patients receiving RR and 4.3 years for those receiving MR (P = .54). Three-year freedom from cytotoxic therapy was 84% for those receiving RR and 95% for those receiving MR (P = .03). The median number of rituximab doses was four patients receiving RR and 18 for those receiving MR. There was no difference in HRQOL. Grade 3 to 4 toxicities were infrequent in both arms. Conclusion In low–tumor burden FL, a re-treatment strategy uses less rituximab while providing disease control comparable to that achieved with a maintenance strategy. PMID:25154829

Identification of Fc Gamma Receptor Glycoforms That Produce Differential Binding Kinetics for Rituximab.

Science.gov (United States)

Hayes, Jerrard M; Frostell, Asa; Karlsson, Robert; Müller, Steffen; Martín, Silvia Míllan; Pauers, Martin; Reuss, Franziska; Cosgrave, Eoin F; Anneren, Cecilia; Davey, Gavin P; Rudd, Pauline M

2017-10-01

Fc gamma receptors (FcγR) bind the Fc region of antibodies and therefore play a prominent role in antibody-dependent cell-based immune responses such as ADCC, CDC and ADCP. The immune effector cell activity is directly linked to a productive molecular engagement of FcγRs where both the protein and glycan moiety of antibody and receptor can affect the interaction and in the present study we focus on the role of the FcγR glycans in this interaction. We provide a complete description of the glycan composition of Chinese hamster ovary (CHO) expressed human Fcγ receptors RI (CD64), RIIa Arg131/His131 (CD32a), RIIb (CD32b) and RIIIa Phe158/Val158 (CD16a) and analyze the role of the glycans in the binding mechanism with IgG. The interactions of the monoclonal antibody rituximab with each FcγR were characterized and we discuss the CHO-FcγRIIIa Phe158/Val158 and CHO-FcγRI interactions and compare them to the equivalent interactions with human (HEK293) and murine (NS0) produced receptors. Our results reveal clear differences in the binding profiles of rituximab, which we attribute in each case to the differences in host cell-dependent FcγR glycosylation. The glycan profiles of CHO expressed FcγRI and FcγRIIIa Phe158/Val158 were compared with the glycan profiles of the receptors expressed in NS0 and HEK293 cells and we show that the glycan type and abundance differs significantly between the receptors and that these glycan differences lead to the observed differences in the respective FcγR binding patterns with rituximab. Oligomannose structures are prevalent on FcγRI from each source and likely contribute to the high affinity rituximab interaction through a stabilization effect. On FcγRI and FcγRIIIa large and sialylated glycans have a negative impact on rituximab binding, likely through destabilization of the interaction. In conclusion, the data show that the IgG1-FcγR binding kinetics differ depending on the glycosylation of the FcγR and further support a

Rapid infusion with rituximab: short term safety in systemic autoimmune diseases

DEFF Research Database (Denmark)

Larsen, Janni Lisander; Jacobsen, Soren

2013-01-01

To describe the incidence, types and severity of adverse events, related to an accelerated regime of rituximab infusion in patients with various autoimmune diseases. Fifty-four patients with systemic autoimmune disease, to be treated with 1,000 mg of rituximab twice 2 weeks apart, participated. Pre......-medication (oral prednisolone, anti-histamine and paracetamol) was administered 1-4 h before infusion start. The first infusion was administered over a period of 195 min. The second infusion over a period of 90 min. Any adverse events were classified using the Clinical Trials Classification of Adverse Events...... (CTCAE) v. 3.0. Ten patients (18.5%) experienced at least one infusion-related reaction (IRR) ever. The first infusion was associated with reactions in 4 CTCAE categories of which rhinitis were the most frequent. The CTCAE severity grading showed six patients (11.1%) had a grade 1 reaction. One patient...

Pregnancies and menstrual function before and after combined radiation (RT) and chemotherapy (TVPP) for Hodgkin's disease

International Nuclear Information System (INIS)

Lacher, M.J.; Toner, K.

1986-01-01

The menstrual cycle, pregnancies, and offspring were evaluated before and after initial combined radiation (RT) and chemotherapy with thiotepa, vinblastine, vincristine, procarbazine, and prednisone (TVPP), in 34 women between the ages of 18 and 44 (median 26.5 years) treated for Stage II and Stage III Hodgkin's disease. The median range of follow-up is 83.1 months (range 40.5-140). After therapy 94.1% (32/34) continued to menstruate. Two of the four patients over the age of 35 ceased to menstruate. All patients under the age of 35 continued to menstruate (30/30). Age at the time of diagnosis was the only factor affecting change in menses with a significant probability (p = .001) that women greater than 30 years of age will experience some change in menstrual pattern. Seventeen pregnancies occurred in 12 women after therapy; 2 had 4 elective abortions; 10 delivered 12 children with normal physical development; 1 will deliver six months from now. Twelve of thirteen patients who wanted to become pregnant have conceived. The ability to become pregnant and deliver normal children after intensive treatment with combined radiation and chemotherapy (RT/TVPP) was comparable to the patients' pretreatment record

Assessment of the Radiation-Equivalent of Chemotherapy Contributions in 1-Phase Radio-chemotherapy Treatment of Muscle-Invasive Bladder Cancer

International Nuclear Information System (INIS)

Plataniotis, George A.; Dale, Roger G.

2014-01-01

Purpose: To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. Methods and Materials: A standard logistic dose–response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. Results: The respective best-fit values of the independent chemotherapy-induced complete response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval −0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. Conclusion: Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy

Efficacy, outcomes, and cost-effectiveness of desensitization using IVIG and rituximab.

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Vo, Ashley A; Petrozzino, Jeffrey; Yeung, Kai; Sinha, Aditi; Kahwaji, Joseph; Peng, Alice; Villicana, Rafael; Mackowiak, John; Jordan, Stanley C

2013-03-27

Transplantation rates are very low for the broadly sensitized patient (panel reactive antibody [PRA]>80%; HS). Here, we examine the efficacy, outcomes, and cost-effectiveness of desensitization using high-dose intravenous immunoglobulin (IVIG) and rituximab to improve transplantation rates in HS patients. From July 2006 to December 2011, 207 HS (56 living donors/151 deceased donors) patients (donor-specific antibody positive, PRA>80%) were desensitized using IVIG and rituximab. After desensitization, responsive patients proceeded to transplantation with an acceptable crossmatch. Cost and outcomes of desensitization were compared with dialysis. Of the 207 treated patients, 146 (71%) were transplanted. At 48 months, patient and graft survival by Kaplan-Meier were 95% and 87.5%, respectively. The total 3-year cost for patients treated in the desensitization arm was $219,914 per patient compared with $238,667 per patient treated in the dialysis arm. Thus, each patient treated with desensitization is estimated to save the U.S. healthcare system $18,753 in 2011 USD. Overall, estimated patient survival at the end of 3 years was 96.6% for patients in the desensitization arm of the model (based on Cedars-Sinai survival rate) compared with 79.0% for an age, end-stage renal disease etiology, and PRA matched group of patients remaining on dialysis during the study period. We conclude that desensitization with IVIG+rituximab is clinically and cost-effective, with both financial savings and an estimated 17.6% greater probability of 3-year survival associated with desensitization versus dialysis alone. However, the benefits of desensitization and transplantation are limited by organ availability and allocation policies.

The value of rituximab treatment in primary Sjögren's syndrome

NARCIS (Netherlands)

Verstappen, Gwenny M.; van Nimwegen, Jolien F.; Vissink, Arjan; Kroese, Frans G. M.; Bootsma, Hendrika

The rationale for B cell depletion therapy with rituximab in primary Sjogren's syndrome relies upon the well-established role of B cell hyperactivity in immunopathogenesis. In line with this notion, several biomarkers of B cell activity are significantly affected by treatment, both in the target

Efficacy and safety of short course adjuvant trastuzumab combination chemotherapy in breast cancer

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Sachin S Hingmire

2017-01-01

Full Text Available Background: The adjuvant short course 9-week trastuzumab combination therapy for human epidermal receptor 2 positive breast cancer patients may often be considered as a cost-effective and safe option and has important implications for the Indian subcontinent as well as other developing countries. However, such regimens of shorter duration trastuzumab therapy like FinHer, offered in view of economic constraints, may not be able to achieve globally comparable cure rates in early breast cancer especially with high-risk women with more than 3 lymph node positive. Methods and Material: Outcome of 21 patients with HER2 positive breast cancer was treated with short course trastuzumab combination chemotherapy in the adjuvant setting was studied. Results: Out of 21 patients 15 are alive and disease free with a follow up of up to 73 months (median follow up 42 months.

Results of preoperative combined therapy with radiation and multi-drug chemotherapy for oral squamous cell carcinomas

International Nuclear Information System (INIS)

Iwai, Masayuki; Sawada, Toshiharu; Furuta, Isao; Sado, Tadashi; Terashima, Ryuichi; Ito, Shigeto

1996-01-01

We retrospectively analyzed the effectiveness of preoperative treatment with combined chemotherapy, including cisplatin (CDDP) and carboplatin (CBDCA), and radiotherapy. Among 19 patients with oral squamous cell carcinoma, the primary site was the tongue in 13, the oral floor in 3, and the maxilla, lip, and gingiva in 1 case each. The clinical stage was 7 cases Stage II, 5 cases Stage III, and 7 cases Stage IV. Chemotherapy was administered intravenously using CDDP 50-80 mg (1 time) or CBDCA 150 mg once a week in a total dose of 300-750 mg, PEP 5 mg twice a week in a total dose of 40-60 mg, and 5-FU or Tegaful 300-600 mg in a total dose of 9.0-18.0 g. Radiotherapy was carried out with Lineac (5 times a week) in a total dose of 20-40 Gy/10-20 f/10-20 days. The clinical response to treatment was evaluated as CR 3 cases, PR 9 cases, and NC 6 cases. The response rate was 12/18 (66.7%) cases. Histologic effectiveness, evaluated according to the classification of Oohoshi and Shimosato, was Grade IV 11 cases, Grade III 3 cases, and Grade II 5 cases. The following adverse reactions were reported: stomatitis 19 cases, fever 13 cases, leukopenia 12 cases, loss of appetite 12 cases, and neutropenia 10 cases. Fourteen of the 19 patients (73.7%) have a good prognosis, without any signs of recurrence or metastasis. The results indicate that multidrug chemotherapy combined with radiotherapy is effective even for highly malignant carcinoma in the oral cavity. (author)

Radio-chemotherapy in advanced tumors of the oral cavity, oro- and hypopharynx

International Nuclear Information System (INIS)

Schmitt, G.; Schnabel, T.

1992-01-01

Among combined radio-chemotherapy regimens of advanced head and neck tumors four modalities can be discriminated: 1. Induction chemotherapy, 2. simultaneous radio-chemotherapy, 3. adjuvant chemotherapy, 4. accelerated-hyperfractionated radiotherapy and chemotherapy. The results of the presently available randomized trials are as follows: 1. Induction chemotherapy has no influence on long-term recurrence-free survival. 2. With respect to simultaneous radio-chemotherapy, recurrence-free survival has been unproved with 5-FU and Mitomycin C. 3. There is evidence that adjuvant cis-platin therapy improves recurrence-free survival. 4. No results are available to date using hyperfractionated accelerated radiotherapy regimens in combination with chemotherapy. (orig.) [de

Comparison of the effects of photon versus carbon ion irradiation when combined with chemotherapy in vitro

International Nuclear Information System (INIS)

Schlaich, Fabian; Brons, Stephan; Haberer, Thomas; Debus, Jürgen; Combs, Stephanie E; Weber, Klaus-Josef

2013-01-01

Characterization of combination effects of chemotherapy drugs with carbon ions in comparison to photons in vitro. The human colon adenocarcinoma cell line WiDr was tested for combinations with camptothecin, cisplatin, gemcitabine and paclitaxel. In addition three other human tumour cell lines (A549: lung, LN-229: glioblastoma, PANC-1: pancreas) were tested for the combination with camptothecin. Cells were irradiated with photon doses of 2, 4, 6 and 8 Gy or carbon ion doses of 0.5, 1, 2 and 3 Gy. Cell survival was assessed using the clonogenic growth assay. Treatment dependent changes in cell cycle distribution (up to 12 hours post-treatment) were measured by FACS analysis after propidium-iodide staining. Apoptosis was monitored for up to 36 hours post-treatment by Nicoletti-assay (with qualitative verification using DAPI staining). All cell lines exhibited the well-known increase of killing efficacy per unit dose of carbon ion exposure, with relative biological efficiencies at 10% survival (RBE 10 ) ranging from 2.3 to 3.7 for the different cell lines. In combination with chemotherapy additive toxicity was the prevailing effect. Only in combination with gemcitabine or cisplatin (WiDr) or camptothecin (all cell lines) the photon sensitivity was slightly enhanced, whereas purely independent toxicities were found with the carbon ion irradiation, in all cases. Radiation-induced cell cycle changes displayed the generally observed dose-dependent G2-arrest with little effect on S-phase fraction for all cell lines for photons and for carbon ions. Only paclitaxel showed a significant induction of apoptosis in WiDr cell line but independent of the used radiation quality. Combined effects of different chemotherapeutics with photons or with carbon ions do neither display qualitative nor substantial quantitative differences. Small radiosensitizing effects, when observed with photons are decreased with carbon ions. The data support the idea that a radiochemotherapy with common

[Anti-EGFR Antibody Combination Chemotherapy Was Effective against Locally Advanced Ascending Colon Cancer as Well as a Recurrent Lesion - A Case Report].

Science.gov (United States)

Yamada, Yasufumi; Yokomizo, Hajime; Yano, Yuki; Okayama, Sachiyo; Satake, Masaya; Ida, Arika; Usui, Takebumi; Yamaguchi, Kentaro; Shiozawa, Shunichi; Yoshimatsu, Kazuhiko; Shimakawa, Takeshi; Katsube, Takao; Naritaka, Yoshihiko; Kato, Hiroyuki

2017-10-01

Here we report a case in which a locally advanced ascending colon cancer was successfully treated with anti-EGFR immunotherapy combined with chemotherapy and curative resection, and recurrent cancer was treated with the same chemotherapy. A 71-year-old man was diagnosed with ascending colon cancer in our department. No distant metastasis was observed, but curative resection was considered impossible because of extensive local cancer invasion. Because a genetic analysis revealed the presence of the wild-type KRAS gene, 6 courses of mFOLFOX6 plus cetuximab were administered. A cPR was obtained and curative resection was performed. The final diagnosis was ypT3N1M0, ypStage III a colon cancer, and chemotherapy improved the cancer stage to Grade 1b. Six courses of FOLFOX6 were then administered, followed by observation. After 2 years 6 months, a tumor of approximately 5 cm in size was noted in the right buttock using surveillance CT and was diagnosed as recurrent colon cancer. We considered further curative resection difficult and therefore 6 courses of mFOLFOX6 plus panitumumab were administered, a cPR was obtained, and right hip tumor extirpation surgery was performed. These results suggest that chemotherapy combined with anti-EGFR antibody immunotherapy is effective in treating recurrent colon cancer.

Refractory myasthenia gravis - clinical profile, comorbidities and response to rituximab.

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Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

2016-01-01

Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27-53 years. In our study 25 patients (32.89%) belonged to the age group of 21-30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA 1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% ( p =3.3x10 -8 ) to 94.6% ( p =2.2x10 -14 ) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA 1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low.

Leuconostoc sp. Meningitis in a Patient Treated with Rituximab for Mantle Cell Lymphoma

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Hrvoje Holik

2015-09-01

Full Text Available We present a 64-year-old man who was treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone chemoimmunotherapy for mantle cell lymphoma and developed purulent meningitis, probably caused by Leuconostoc sp. The patient had severe hypogammaglobulinemia, which is a possible complication of rituximab therapy. To our knowledge and after reviewing the available medical literature, this is the first described case of purulent meningitis caused by Leuconostoc sp. in a patient with mantle cell lymphoma that appeared after treatment with the R-CHOP protocol. The diagnosis of purulent meningitis was based on clinical, laboratory and cytological cerebrospinal fluid findings, in addition to blood culture results in which we isolated Leuconostoc sp. The patient was treated with meropenem with full recovery.

Limited Chemotherapy and Shrinking Field Radiotherapy for Osteolymphoma (Primary Bone Lymphoma): Results From the Trans-Tasman Radiation Oncology Group 99.04 and Australasian Leukaemia and Lymphoma Group LY02 Prospective Trial

International Nuclear Information System (INIS)

Christie, David; Dear, Keith; Le, Thai; Barton, Michael; Wirth, Andrew; Porter, David; Roos, Daniel; Pratt, Gary

2011-01-01

Purpose: To establish benchmark outcomes for combined modality treatment to be used in future prospective studies of osteolymphoma (primary bone lymphoma). Methods and Materials: In 1999, the Trans-Tasman Radiation Oncology Group (TROG) invited the Australasian Leukemia and Lymphoma Group (ALLG) to collaborate on a prospective study of limited chemotherapy and radiotherapy for osteolymphoma. The treatment was designed to maintain efficacy but limit the risk of subsequent pathological fractures. Patient assessment included both functional imaging and isotope bone scanning. Treatment included three cycles of CHOP chemotherapy and radiation to a dose of 45 Gy in 25 fractions using a shrinking field technique. Results: The trial closed because of slow accrual after 33 patients had been entered. Accrual was noted to slow down after Rituximab became readily available in Australia. After a median follow-up of 4.3 years, the five-year overall survival and local control rates are estimated at 90% and 72% respectively. Three patients had fractures at presentation that persisted after treatment, one with recurrent lymphoma. Conclusions: Relatively high rates of survival were achieved but the number of local failures suggests that the dose of radiotherapy should remain higher than it is for other types of lymphoma. Disability after treatment due to pathological fracture was not seen.

Analysis of Perioperative Chemotherapy in Resected Pancreatic Cancer: Identifying the Number and Sequence of Chemotherapy Cycles Needed to Optimize Survival.

Science.gov (United States)

Epelboym, Irene; Zenati, Mazen S; Hamad, Ahmad; Steve, Jennifer; Lee, Kenneth K; Bahary, Nathan; Hogg, Melissa E; Zeh, Herbert J; Zureikat, Amer H

2017-09-01

Receipt of 6 cycles of adjuvant chemotherapy (AC) is standard of care in pancreatic cancer (PC). Neoadjuvant chemotherapy (NAC) is increasingly utilized; however, optimal number of cycles needed alone or in combination with AC remains unknown. We sought to determine the optimal number and sequence of perioperative chemotherapy cycles in PC. Single institutional review of all resected PCs from 2008 to 2015. The impact of cumulative number of chemotherapy cycles received (0, 1-5, and ≥6 cycles) and their sequence (NAC, AC, or NAC + AC) on overall survival was evaluated Cox-proportional hazard modeling, using 6 cycles of AC as reference. A total of 522 patients were analyzed. Based on sample size distribution, four combinations were evaluated: 0 cycles = 12.1%, 1-5 cycles of combined NAC + AC = 29%, 6 cycles of AC = 25%, and ≥6 cycles of combined NAC + AC = 34%, with corresponding survival. 13.1, 18.5, 37, and 36.8 months. On MVA (P cycles AC, receipt of 0 cycles [HR 3.57, confidence interval (CI) 2.47-5.18] or 1-5 cycles in any combination (HR 2.37, CI 1.73-3.23) was associated with increased hazard of death, whereas receipt of ≥6 cycles in any sequence was associated with optimal and comparable survival (HR 1.07, CI 0.78-1.47). Receipt of 6 or more perioperative cycles of chemotherapy either as combined neoadjuvant and adjuvant or adjuvant alone may be associated with optimal and comparable survival in resected PC.

Time-Dependent Structural Alteration of Rituximab Analyzed by LC/TOF-MS after a Systemic Administration to Rats.

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Yuki Otani

Full Text Available Therapeutic monoclonal antibodies (mAbs have heterogeneities in their structures. Multiple studies have reported that the variety of post-translational modifications could affect the pharmacokinetic profiles or pharmacological potencies of therapeutic mAbs. Taking into the account that the structural modification of mAbs would affect the efficacy, it is worth investigating the structural alteration of therapeutic mAbs in the blood and the relationship between their structures and pharmacological effects. Herein, we have developed the method to isolate rituximab from plasma in which endogenous IgGs interfere the detection of rituximab, and successfully developed the analytical method with a liquid chromatograph time-of-flight mass spectrometer to detect the structure of rituximab in plasma with errors less than 30 parts per millions. Eight types of carbohydrate chains in rituximab were detected by this method. Interestingly, time-dependent changes in carbohydrate chains such as AAF (G2F and GnGn (G0 were observed in rats, although the amino acids were stable. Additionally, these structural changes were observed via incubation in plasma as in the rat experiment, suggesting that a certain type of enzyme in plasma caused the alterations of the carbohydrate chains. The present analytical methods could clarify the actual pharmacokinetics of therapeutic mAbs, and help to evaluate the interindividual variations in pharmacokinetics and efficacy.

Granulocyte colony stimulating factor priming chemotherapy is more effective than standard chemotherapy as salvage therapy in relapsed acute myeloid leukemia.

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Shen, Ying; He, Aili; Wang, Fangxia; Bai, Ju; Wang, Jianli; Zhao, Wanhong; Zhang, Wanggang; Cao, Xingmei; Chen, Yinxia; Liu, Jie; Ma, Xiaorong; Chen, Hongli; Feng, Yuandong; Yang, Yun

2017-12-29

To improve the complete remission (CR) rate of newly diagnosed acute myeloid leukemia (AML) patients and alleviate the severe side effects of double induction chemotherapy, we combined a standard regimen with granulocyte colony-stimulating factor (G-CSF) priming chemotherapy to compose a new double induction regimen for AML patients who failed to achieve CR after the first course. Ninety-seven patients with AML who did not achieve CR after the first course of standard chemotherapy were enrolled. Among them, 45 patients received G-CSF priming combined with low-dose chemotherapy during days 20-22 of the first course of chemotherapy, serving as priming group, 52 patients were administered standard chemotherapy again, serving as control group. Between the two groups there were no differences in the French-American-British (FAB) classification, risk status, the first course of chemotherapy, blood cell count or blasts percentage of bone marrow before the second course. But the CR rate was significantly higher and the adverse effect was much lower in the priming group than the control group. Cox multivariate regression analysis showed that WBC level before the second course and the selection of the second chemotherapy regimen were two independent factors for long survival of patients. These results elucidate that standard chemotherapy followed by G-CSF priming new double induction chemotherapy is an effective method for AML patients to improve CR rate and reduce adverse effects. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Effectiveness of combinations of Ayurvedic drugs in alleviating drug toxicity and improving quality of life of cancer patients treated with chemotherapy.

Science.gov (United States)

Deshmukh, Vineeta; Kulkarni, Arvind; Bhargava, Sudhir; Patil, Tushar; Ramdasi, Vijay; Gangal, Sudha; Godse, Vasanti; Datar, Shrinivas; Gujar, Shweta; Sardeshmukh, Sadanand

2014-11-01

This study was conducted to assess the effectiveness of combinations of Ayurvedic drugs in alleviating the toxicity of chemotherapy and improving the quality of life of cancer patients. The following was the research question: Can Ayurvedic drugs be used to alleviate the side effects of chemotherapy and improve the quality of life of cancer patients? Random patients with malignancies of different tissues, grades, and stages were divided into two groups according to their treatment modality. Group 1 consisted of 15 patients treated with six cycles of chemotherapy alone and who did not receive any Ayurvedic drugs (control group). Group 2 consisted of patients (divided into three arms) who received Ayurvedic drugs during chemotherapy and after chemotherapy. Nineteen patients in arm 1 received the Ayurvedic drugs Mauktikyukta Kamdudha (MKD) and Mauktikyukta Praval Panchamruta (MPP) along with a full course of chemotherapy. Fifteen patients in arm 2 received the same Ayurvedic treatment, but the treatment was started after completing the sixth cycle of chemotherapy. Eighteen patients in arm 3 received the Suvarnabhasmadi formulation (SBD) in addition to MKD and MPP after completing the sixth cycle of chemotherapy. Treatment was given for 16 weeks in all three arms. Patients from both groups were observed for a period of 6 months. The assessment criteria depended on Common Toxicity Criteria (CTC designed by NIH and NCI): haemogram; weight; physical examination including Quality of Life Questionnaire (QLQ designed by the European Organization of Research and Treatment of Cancer (EORTC)) for functional, symptom and global scores; and Karnofsky score for assessment of general well-being and activities of daily life. ECOG (Eastern Cooperation Oncology Group) score was also additionally included for assessment of symptoms. From amongst the symptomatic criteria, there was significant improvement in all the three arms compared with the control group in nausea, loss of appetite

Optimization of combination chemotherapy based on the calculation of network entropy for protein-protein interactions in breast cancer cell lines

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Carels Nicolas

2015-12-01

We propose several novel drug combinations using only the approved drugs for the inactivation of the target identified in this study with the purpose of increasing patient survival and lowering the deleterious side effects of cancer chemotherapy.

[Treatment of Chemotherapy Related Leukocytopenia by Oral Administration of Multiple Leucogenic Drugs Combined with G-CSF: an Experimental Study].

Science.gov (United States)

Zhang, Xi-ping; Zhang, Xiang; Yang, Hong-jian; Zou, De-hong; He, Xiang-ming; Yu, Xing-fei; Li, Yong-feng

2015-07-01

To evaluate efficacies of three commonly used oral drugs including Berbamine Hydrochloride Tablet (B), Qijiao Shengbai Capsule (Q), and Leucogen Tablet (L) (by single drug, two drugs or three drugs) combined with granulocyte colony-stimulating factor (G-CSF) for treat ment of chemotherapy related leukocytopenia in mice. Totally 156 Kunming male mice were divided into the normal control group (A, n=24), the model group (B, n=24), the G-CSF group (C, n =24), the G-CSF+Q group (D, n=12), G-CSF+ B (E, n=12), the G-CSF+L group (F, n=12), the G-CSF + Q + B group (G, n=12), the G-CSF + Q + L group (H, n=12), the G-CSF + L + B group (I, n=12), and the G-CSF + L + Q + B (J, n=12). Mouse models of chemotherapy related leukocytopenia were established by intraperitoneal injection of cyclophosphamide (CTX). A G-CSF group was set up as a positive control. Mice were treated by a single oral drug, a single oral drug combined with G-CSF, and two or three drugs combined with G-CSF respectively, and the death rate calculated. Hemocytes [such as white blood cells (WBC) and its classification, red blood cells (RBC), platelet (PLT), hemoglobin (Hb)] were calculated by hematology analyzer. Mice were anatomized and important organs weighed. Organ indices were calculated. There was no statistical difference in the mortality rate among all groups (P > 0.05). Compared with Group B, WBC was elevated in all other groups (P drug B and L (P chemotherapy related leukopenia or decreased three blood series was to administrate three commonly oral drugs combined with G-CSF. Authors speculated that G-CSF and Q might have a certain effect on CTX induced immune inhibition.

High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

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L John Hoffer

Full Text Available Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type

High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

Science.gov (United States)

Hoffer, L John; Robitaille, Line; Zakarian, Robert; Melnychuk, David; Kavan, Petr; Agulnik, Jason; Cohen, Victor; Small, David; Miller, Wilson H

2015-01-01

Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail. We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement. Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy

The study of combination therapy for arterial infusion chemotherapy and radiation therapy in unresectable gallbladder cancer

International Nuclear Information System (INIS)

Goto, Takuma; Saito, Hiroya; Yanagawa, Nobuyuki; Fujinaga, Akihiro; Saito, Yoshinori

2013-01-01

In this study, we investigated an effective strategy of treatment for unresectable gallbladder cancer (GBC) by the retrospective analysis of prognostic factors and anti-tumor therapies, especially combination therapy of arterial infusion chemotherapy and radiation therapy (AI+PT). Forty-three patients with unresectable GBC were enrolled, and prognostic factors were investigated by multivariate analysis using a proportional hazard model. In addition, we examined the indication and after-therapy by analyzing the each factor cumulative survival rates and anti-tumor effect about the AI + RT group (n=24). AI + RT and the responders to the first-line therapy were significant prognostic factors. In AI + RT group, median survival time, progression-free survival and the 1-year survival rate, the response and disease control rates was 15.5 months, 7.1 months, 62.5%. 54.2% and 95.8%, respectively; which suggested prolonged survival and high anti-tumor effect. Cumulative survival rate was significantly shorter in cases with distant metastasis except liver metastases, and has been tendency to extend in the group who underwent systemic chemotherapy as after-therapy. The treatment strategy, using the Al + RT as first-line with the systemic chemotherapy as after-therapy, suggested contribute to the prolonged survival in locally advanced and liver metastases cases of GBC. (author)

Estimated radiation pneumonitis risk after photon versus proton therapy alone or combined with chemotherapy for lung cancer

DEFF Research Database (Denmark)

Vogelius, Ivan R.; Westerly, David C; Aznar, Marianne Camille

2011-01-01

Background. Traditionally, radiation therapy plans are optimized without consideration of chemotherapy. Here, we model the risk of radiation pneumonitis (RP) in the presence of a possible interaction between chemotherapy and radiation dose distribution. Material and methods. Three alternative......-radiation combinations could be an interesting indication for selecting patients for proton therapy. It is likely that the IMRT plans would perform better if the CERD was accounted for during optimization, but more clinical data is required to facilitate evidence-based plan optimization in the multi-modality setting....... treatment plans are compared in 18 non-small cell lung cancer patients previously treated with helical tomotherapy; the tomotherapy plan, an intensity modulated proton therapy plan (IMPT) and a three dimensional conformal radiotherapy (3D-CRT) plan. All plans are optimized without consideration...

Multimodal treatment combining chemotherapy, hyperthermia and radiotherapy for ovarian cancer

International Nuclear Information System (INIS)

Nagashima, Kei

1992-01-01

There has been increasing interest in the use of heat in the treatment of cancer. Theoretically cells are the most sensitive to ionizing radiation at mitosis, whereas the cycle phase that is the most resistant to ionizing radiation namely late in the DNA. Synthetic phase (late S) is the most sensitive to hyperthermia. Hyperthermia has been reported to enhance the cytocidal effects of several active chemotherapeutic agents. When thermal potentiation of chemotherapeutic agents against malignant cells is contemplated, normal tissues have a relatively high ambient blood flow which increases in response to thermal stress, thereby dissipating heat, compared to tumors. Tumors, with relatively poor blood flow and a responsive neovasculature, are in capable of augmenting flow and acting as a heat reservoir. This is the phenomenon of a heat reservoir which is one factor to enhance the cytocidal effects of several active anticancer agents for enhancing the uptake in tumor. The importance is in the adjuvant chemotherapy treated for post operative, advanced and recurrent ovarian cancer. Heating enhances the effects of radiotherapy and chemotherapy. Thirty patients with ovarian cancer were subjected to the multidisciplinary treatment with combination of hyperthermochemotherapy and radiation. The 30 patients consisted of 18 with endometrioid adenocarcinoma and 7 with serious post operative or recurrent status. Two types of equipments with rediofrequencies of 70 MHz (BSD-1000) or 434 MHZ (TAG MED·HS 434) were used for hyperthermia. Chemotherapeutic agents such as adriamycin, cis DDP, cyclophosphamide and etoposide were injected intravenously. Arterial infusion with reservoir was very effective in advanced stage of ovarian cancer. No severe or fatal side effects were observed. Hyperthermochemotherapy is useful and effective for the postoperative management or the treatment of recurrent cancer of the ovary. (J.P.N.)

Nanotechnology for Cancer Therapy Based on Chemotherapy

OpenAIRE

Chen-Yang Zhao; Rui Cheng; Zhe Yang; Zhong-Min Tian

2018-01-01

Chemotherapy has been widely applied in clinics. However, the therapeutic potential of chemotherapy against cancer is seriously dissatisfactory due to the nonspecific drug distribution, multidrug resistance (MDR) and the heterogeneity of cancer. Therefore, combinational therapy based on chemotherapy mediated by nanotechnology, has been the trend in clinical research at present, which can result in a remarkably increased therapeutic efficiency with few side effects to normal tissues. Moreover,...

The effect of resveratrol in combination with irradiation and chemotherapy. Study using Merkel cell carcinoma cell lines

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Heiduschka, G. [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Vienna (Austria); Medical University of Vienna, Clinical Pharmacology, Vienna (Austria); Lill, C.; Brunner, M.; Thurnher, D. [Medical University of Vienna, Department of Otorhinolaryngology, Head and Neck Surgery, Vienna (Austria); Seemann, R. [Medical University of Vienna, Maxillo-Facial Surgery, Vienna (Austria); Schmid, R. [Medical University of Vienna, Radiotherapy and -biology, Vienna (Austria); Houben, R. [University Hospital Wuerzburg, Department of Dermatology, Wuerzburg (Germany); Bigenzahn, J. [CeMM-Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna (Austria)

2014-01-15

Merkel cell carcinoma (MCC) is a rare, but highly malignant tumor of the skin. In case of systemic disease, possible therapeutic options include irradiation or chemotherapy. The aim of this study was to evaluate whether the flavonoid resveratrol enhances the effect of radiotherapy or chemotherapy in MCC cell lines. The two MCC cell lines MCC13 and MCC26 were treated with increasing doses of resveratrol. Combination experiments were conducted with cisplatin and etoposide. Colony forming assays were performed after sequential irradiation with 1, 2, 3, 4, 6, and 8 Gy and apoptosis was assessed with flow cytometry. Expression of cancer drug targets was analyzed by real-time PCR array. Resveratrol is cytotoxic in MCC cell lines. Cell growth is inhibited by induction of apoptosis. The combination with cisplatin and etoposide resulted in a partially synergistic inhibition of cell proliferation. Resveratrol and irradiation led to a synergistic reduction in colony formation compared to irradiation alone. Evaluation of gene expression did not show significant difference between the cell lines. Due to its radiosensitizing effect, resveratrol seems to be a promising agent in combination with radiation therapy. The amount of chemosensitizing depends on the cell lines tested. (orig.) [German] Das Merkelzellkarzinom (MCC) ist ein seltener, jedoch hochmaligner Tumor der Haut. Sowohl Strahlentherapie oder Chemotherapie sind moegliche therapeutische Optionen. In dieser Studie wurde untersucht, ob das Flavonoid Resveratrol die Wirkung der Strahlen- oder Chemotherapie in MCC-Zelllinien verbessert. Die beiden MCC-Zelllinien MCC13 und MCC26 wurden mit ansteigenden Dosen von Resveratrol behandelt. Kombinationsexperimente wurden mit Cisplatin und Etoposid durchgefuehrt und die Koloniebildung in ''Colony-Forming''-Assays nach erfolgter sequentieller Bestrahlung mit 1, 2, 3, 4, 6 und 8 Gy gemessen. Desweiteren wurde die Apoptose mittels Durchflusszytometrie bestimmt. Die

[Long-term Efficacy of Radiofrequency Ablation Combined with Chemotherapy 
in the Treatment of Patients with Advanced Non-small Cell Lung Cancer
--A Retrospective Study].

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Du, Shuhui; Qin, Da; Pang, Ruiqi; Zhang, Yeqing; Zhao, Siqi; Hu, Mu; Zhi, Xiuyi

2017-10-20

Radiofrequency ablation (RFA) combined with chemotherapy has a certain short-term therapeutic effect for the treatment of advanced non-small cell lung cancer (NSCLC), but whether it can improve the long-term survival rate of patients is still controversy. This study retrospectively analyzed the difference of long-term efficacy between RFA combined with chemotherapy and chemotherapy alone in the treatment of patients with advanced NSCLC. A total of 77 patients with stage IIIb and stage IV NSCLC who underwent radiofrequency ablation and chemotherapy in the Department of Thoracic Surgery, Xuanwu Hospital, Capital University of Medical Sciences from September 2009 to December 2015 were enrolled as the treatment group. Chemotherapy with no radiofrequency ablation was performed in 56 patients with stage IIIb and stage IV NSCLC as the control group. Two groups of patients were followed up by telephone about their living conditions. "Survival" package of R software version 3.4.1 was used for statistical analysis. Two sets of data baseline levels were tested by chi-square test. The bias was processed by Cox regression model and the survival curve was plotted using covariate mean substitution method. The first-year survival rate of the treatment group was 70.74%, the two-year survival rate was 39.31% and the median survival time was 22.1 months. The one-year survival rate was 54.54% in the control group, the two-year survival rate was 19.49%, the median survival for 18.1 months. The long-term survival rate of the treatment group was better than that of the control group (PRadiofrequency ablation of lung cancer combined with chemotherapy can significantly improve the 2-year survival rate of patients with stage IIIb and stage IV NSCLC.

Gemcitabine and S-1 Combination Chemotherapy in Patients with Advanced Biliary Tract Cancer:A Retrospective Study

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Kazuhito Mita

2010-12-01

Full Text Available Background:The aim of this study was to investigate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer. Patients and Methods: A retrospective study was performed on 15 consecutive patients. Gemcitabine was administered intravenously at 1,000 mg/m2 on days 8 and 15. Oral S-1 (60 mg/m2 in 2 divided doses was given daily for the first 2 weeks, followed by 1 week of rest. This 3-week course of treatment was repeated. The primary endpoint was response rate, and the secondary endpoints were overall survival, progression-free survival, and safety. Results: The overall response rate was 26.7%, and the disease control rate was 73.4%. The overall survival was 12.0 months (95% CI, 9.5–14.5 months, and the progression-free survival was 8.0 months (95% CI, 4.3–11.7 months. Adverse events of grade 3 or 4 occurred in 33.3%, and the major grade 3/4 toxicities were anemia (20.0%, leukopenia (13.3%, and anorexia (13.3%. Conclusion:Gemcitabine and S-1 combination chemotherapy is effective and safe in patients with advanced biliary tract cancer.

Randomized study: small cell anaplastic lung cancer treated by combination chemotherapy and adjuvant radiotherapy

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Fox, R.M.; Woods, R.L.; Brodie, G.N.; Tattersall, M.H.N.

1980-01-01

Chemotherapy and primary site radiation therapy were compared to chemotherapy alone in a randomized study of 125 patients with small cell cancer of the lung. The sites of initial relapse, as well as disease free and overall survival were analyzed. Radiotherapy to the primary site reduced the rate of local relapse, but median survival was not prolonged in patients with either limited or extensive disease, when the radiation therapy-chemotherapy group was compared to the group that received chemotherapy alone

[Early detection of the cardiotoxicity induced by chemotherapy drug through two-dimensional speckle tracking echocardiography combined with high-sensitive cardiac troponin T].

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Wang, W; Kang, Y; Shu, X H; Shen, X D; He, B

2017-11-23

Objective: To investigate the clinical value of two-dimensional speckle tracking echocardiography(2D-STE) combined with high-sensitive cardiac troponin T (hs-cTnT) in early detection of the cardiotoxicity induced by chemotherapy drug. Methods: Seventy-five non-Hodgkin's lymphoma patients who received the CHOP regimen were recruited in this study. Conventional echocardiography and 2D-STE were performed on these patients before chemotherapy, the second day after the third course of chemotherapy (during chemotherapy) and the second day after the last course of chemotherapy (after chemotherapy). The parameters included left ventricular ejection fraction (LVEF), global longitudinal strain (LS), global circumferential strain (CS) and global radial strain (RS). The serum hs-cTNT levels were tested simultaneously. Results: Three cycles of CHOP were completed in 30 patients and 6-8 cycles of CHOP were completed in 45 patients. The LVEF of 75 patients before, during and after chemotherapy was (63.8±2.6)%, (63.8±2.8)% and (64.0±3.3)%, respectively, without significant difference ( P =0.91). However, the LS of 75 patients before, during and after chemotherapy was (-18.5±1.7)%, (-16.5±1.9)% and (-16.0±1.6)%, respectively. The CS was (-20.9±2.9)%, (-19.3±3.5)% and (-19.2±3.2)%, respectively. The RS was (39.2±6.4)%, (35.3±5.2)% and (35.0±6.2)%, respectively. The hs-cTnT was (0.001 0±0.002 0)ng/ml, (0.006 3±0.008 9)ng/ml and (0.007 3±0.003 8)ng/ml, respectively. The LS, CS and RS were significantly decreased while hs-cTnT was significantly increased during chemotherapy when compared to those before chemotherapy (all of P chemotherapy were marginally different from those during chemotherapy (all of P >0.05). Moreover, T(LS-SD), T(CS-SD) and T(RS-SD) showed no significant difference before, during and after chemotherapy (all of P >0.05). The reduction of LS was positively associated with the enhancement of hs-cTnT after chemotherapy ( r =0.60, P effectively and

Long-term Follow-up of Treatment with Ibrutinib and Rituximab in Patients with High-Risk Chronic Lymphocytic Leukemia.

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Jain, Preetesh; Keating, Michael J; Wierda, William G; Sivina, Mariela; Thompson, Philip A; Ferrajoli, Alessandra; Estrov, Zeev; Kantarjian, Hagop; O'Brien, Susan; Burger, Jan A

2017-05-01

Background: Ibrutinib is an active therapy with an acceptable safety profile for patients with chronic lymphocytic leukemia (CLL), including high-risk patients with del17p or with TP53 mutations. Ibrutinib is broadly indicated for the treatment of patients with CLL and specifically including those with 17p deletion. The optimal use of ibrutinib in combination with other agents remains controversial. Experimental Design: We report the long-term outcome [median follow-up of 47 months (range, 36-51 months)] of 40 patients with high-risk CLL, treated on the first ibrutinib combination trial with rituximab (IR). The majority of patients (36/40) were previously treated. Results: Median age was 65 years, and 21 patients (52%) had 17p deletion. Median duration on treatment was 41 months (range, 2-51 months), and median number of treatment cycles was 42 (range, 2-49). Overall response rate was 95%, and 9 patients (23%) attained a complete remission. Twenty-one patients discontinued treatment, 10 due to disease progression, 9 for other causes, and 2 due to stem cell transplantation; the remaining 19 patients continue on ibrutinib. Median progression-free survival for all patients was 45 months, which was significantly shorter in the subgroup of patients with del17p ( n = 21, 32.3 months, P = 0.02). Fourteen patients (35%) died, five from progressive disease, five from infections, and four from other causes. Median overall survival has not been reached. Conclusions: IR combination therapy leads to durable remissions in high-risk CLL; the possible benefit from the addition of rituximab is currently explored in a randomized trial. Clin Cancer Res; 23(9); 2154-8. ©2016 AACR . ©2016 American Association for Cancer Research.

Neoadjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: Defining high-risk patients who may benefit before concurrent chemotherapy combined with intensity-modulated radiotherapy.

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Du, Xiao-Jing; Tang, Ling-Long; Chen, Lei; Mao, Yan-Ping; Guo, Rui; Liu, Xu; Sun, Ying; Zeng, Mu-Sheng; Kang, Tie-Bang; Shao, Jian-Yong; Lin, Ai-Hua; Ma, Jun

2015-11-13

The purpose of this study was to create a prognostic model for distant metastasis in patients with locally advanced NPC who accept concurrent chemotherapy combined with intensity-modulated radiotherapy (CCRT) to identify high-risk patients who may benefit from neoadjuvant chemotherapy (NACT). A total of 881 patients with newly-diagnosed, non-disseminated, biopsy-proven locoregionally advanced NPC were retrospectively reviewed; 411 (46.7%) accepted CCRT and 470 (53.3%) accepted NACT followed by CCRT. Multivariate analysis demonstrated N2-3 disease, plasma Epstein-Barr virus (EBV) DNA > 4000 copies/mL, serum albumin ≤ 46 g/L and platelet count >300 k/cc were independent prognostic factors for distant metastasis in the CCRT group. Using these four factors, a prognostic model was developed, as follows: 1) low-risk group: 0-1 risk factors; and 2) high-risk group: 2-4 risk factors. In the high-risk group, patients who accepted NACT + CCRT had significantly higher distant metastasis-free survival and progression-free survival rates than the CCRT group (P = 0.001; P = 0.011). This simple prognostic model for distant metastasis in locoregionally advanced NPC may facilitate with the selection of high-risk patients who may benefit from NACT prior to CCRT.

Chemotherapy and Radiofrequency-Induced Mild Hyperthermia Combined Treatment of Orthotopic Pancreatic Ductal Adenocarcinoma Xenografts.

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Krzykawska-Serda, Martyna; Agha, Mahdi S; Ho, Jason Chak-Shing; Ware, Matthew J; Law, Justin J; Newton, Jared M; Nguyen, Lam; Curley, Steven A; Corr, Stuart J

2018-04-02

Patients with pancreatic ductal adenocarcinomas (PDAC) have one of the poorest survival rates of all cancers. The main reason for this is related to the unique tumor stroma and poor vascularization of PDAC. As a consequence, chemotherapeutic drugs, such as nab-paclitaxel and gemcitabine, cannot efficiently penetrate into the tumor tissue. Non-invasive radiofrequency (RF) mild hyperthermia treatment was proposed as a synergistic therapy to enhance drug uptake into the tumor by increasing tumor vascular inflow and perfusion, thus, increasing the effect of chemotherapy. RF-induced hyperthermia is a safer and non-invasive technique of tumor heating compared to conventional contact heating procedures. In this study, we investigated the short- and long-term effects (~20 days and 65 days, respectively) of combination chemotherapy and RF hyperthermia in an orthotopic PDAC model in mice. The benefit of nab-paclitaxel and gemcitabine treatment was confirmed in mice; however, the effect of treatment was statistically insignificant in comparison to saline treated mice during long-term observation. The benefit of RF was minimal in the short-term and completely insignificant during long-term observation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Combined photothermal-chemotherapy of breast cancer by near infrared light responsive hyaluronic acid-decorated nanostructured lipid carriers

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Zheng, Shaohui; Du Nguyen, Van; Song, Seung Yoon; Han, Jiwon; Park, Jong-Oh

2017-10-01

In this study, a novel type of hyaluronic acid (HA)-decorated nanostructured lipid carrier (NLC) was prepared and investigated as a light-triggered drug release and combined photothermal-chemotherapy for cancer treatment. Polyhedral gold nanoparticles (Au NPs) with an average size of 10 nm were synthesized and co-encapsulated with doxorubicin (DOX) in the matrix of NLCs with a high drug loading efficiency (above 80%). HA decoration was achieved by the electrostatic interaction between HA and CTAB on the NLC surface. A remarkable temperature increase was observed by exposing the Au NP-loaded NLCs to an NIR laser, which heated the samples sufficiently (above 40 °C) to kill tumor cells. The entrapped DOX exhibited a sustained, stepwise NIR laser-triggered drug release pattern. The biocompatibility of the NLCs was investigated by MTT assay and the cell viability was maintained above 85%, even at high concentrations. The intracellular uptake of free DOX and entrapped DOX, observed by confocal microscopy, revealed two distinct uptake mechanisms, i.e. passive diffusion and endocytosis, respectively. In particular, internalization of the HA-Au-DOX-NLCs was more extensively enhanced than the Au-DOX-NLCs, which was attributed to HA-CD44 receptor-mediated endocytosis. Meanwhile, the internalized NLCs successfully escaped from the lysosomes, increasing the intracellular DOX. The HA-Au-DOX-NLCs IC50 value decreased from 2.3 to 0.6 μg ml-1 with NIR irradiation at 72 h, indicating the excellent synergistic antitumor effect of photothermal-chemotherapy. The photothermal ablation was further confirmed by a live/dead cell staining assay. Thus, a combined photothermal-chemotherapy approach has been proposed as a promising strategy for cancer treatment.

Efficacy of S-1 plus nedaplatin compared to standard second-line chemotherapy in EGFR-negative lung adenocarcinoma after failure of first-line chemotherapy.

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Tang, Yu; Wang, Wei; Teng, Xiu-Zhi; Shi, Lin

2014-09-01

For patients with advanced non-small cell lung adenocarcinoma that fail to respond to first-line chemotherapy and that do not involve epidermal growth factor receptor (EGFR) mutations, previous empirical analysis showed that a single second-line chemotherapy agent may be inadequate for the control of further tumor development. This study examines the combination of S-1 drugs and nedaplatin that has no cross-resistance to first-line treatments; 179 cases of IIIb-IV stage non-small-cell lung adenocarcinoma that failed to respond to first-line chemotherapy were included, and these subjects did not have mutated EGFRs. In the present study, S-1 plus nedaplatin chemotherapy was better than standard second-line chemotherapy options in the treatment of advanced lung adenocarcinoma that did not involve EGFR mutations and that failed to respond to first-line chemotherapy. Additionally, the combination of S-1 and nedaplatin seemed to be well tolerated, making this chemotherapy technique a potentially strong candidate for the treatment of advanced non-small-cell lung adenocarcinoma.

Posterior reversible encephalopathy syndrome masquerading as progressive multifocal leukoencephalopathy in rituximab treated neuromyelitis optica.

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Berger, Joseph R; Neltner, Janna; Smith, Charles; Cambi, Franca

2014-11-01

Both progressive multifocal leukoencephalopathy (PML) and posterior reversible encephalopathy syndrome (PRES) have been reported as complications of rituximab therapy. These disorders may appear indistinguishable on magnetic resonance imaging (MRI). We report on a 42 year old woman with neuromyelitis optica (NMO) of 10 years duration who developed extensive white matter disease affecting chiefly both parietal lobes 6 months after her first and only dose of rituximab. The MRI findings suggested the diagnosis of PML, but her history was more consistent with PRES. Ultimately, a brain biopsy was performed which was consistent with the diagnosis of PRES. PRES and PML may have overlapping symptomatology and be indistinguishable on MRI. An approach to distinguishing between these two disorders is addressed. Copyright © 2014. Published by Elsevier B.V.

Safety and feasibility of fasting in combination with platinum-based chemotherapy.

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Dorff, Tanya B; Groshen, Susan; Garcia, Agustin; Shah, Manali; Tsao-Wei, Denice; Pham, Huyen; Cheng, Chia-Wei; Brandhorst, Sebastian; Cohen, Pinchas; Wei, Min; Longo, Valter; Quinn, David I

2016-06-10

Short-term starvation prior to chemotherapy administration protects mice against toxicity. We undertook dose-escalation of fasting prior to platinum-based chemotherapy to determine safety and feasibility in cancer patients. 3 cohorts fasted before chemotherapy for 24, 48 and 72 h (divided as 48 pre-chemo and 24 post-chemo) and recorded all calories consumed. Feasibility was defined as ≥ 3/6 subjects in each cohort consuming ≤ 200 kcal per 24 h during the fast period without excess toxicity. Oxidative stress was evaluated in leukocytes using the COMET assay. Insulin, glucose, ketones, insulin-like growth factor-1 (IGF-1) and IGF binding proteins (IGFBPs) were measured as biomarkers of the fasting state. The median age of our 20 subjects was 61, and 85 % were women. Feasibility criteria were met. Fasting-related toxicities were limited to ≤ grade 2, most commonly fatigue, headache, and dizziness. The COMET assay indicated reduced DNA damage in leukocytes from subjects who fasted for ≥48 h (p = 0.08). There was a non-significant trend toward less grade 3 or 4 neutropenia in the 48 and 72 h cohorts compared to 24 h cohort (p = 0.17). IGF-1 levels decreased by 30, 33 and 8 % in the 24, 48 and 72 h fasting cohorts respectively after the first fasting period. Fasting for 72 h around chemotherapy administration is safe and feasible for cancer patients. Biomarkers such as IGF-1 may facilitate assessment of differences in chemotherapy toxicity in subgroups achieving the physiologic fasting state. An onging randomized trial is studying the effect of 72 h of fasting. NCT00936364 , registered propectively on July 9, 2009.

Safety and feasibility of fasting in combination with platinum-based chemotherapy

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Dorff, Tanya B.; Groshen, Susan; Garcia, Agustin; Shah, Manali; Tsao-Wei, Denice; Pham, Huyen; Cheng, Chia-Wei; Brandhorst, Sebastian; Cohen, Pinchas; Wei, Min; Longo, Valter; Quinn, David I.

2016-01-01

Short-term starvation prior to chemotherapy administration protects mice against toxicity. We undertook dose-escalation of fasting prior to platinum-based chemotherapy to determine safety and feasibility in cancer patients. 3 cohorts fasted before chemotherapy for 24, 48 and 72 h (divided as 48 pre-chemo and 24 post-chemo) and recorded all calories consumed. Feasibility was defined as ≥ 3/6 subjects in each cohort consuming ≤ 200 kcal per 24 h during the fast period without excess toxicity. Oxidative stress was evaluated in leukocytes using the COMET assay. Insulin, glucose, ketones, insulin-like growth factor-1 (IGF-1) and IGF binding proteins (IGFBPs) were measured as biomarkers of the fasting state. The median age of our 20 subjects was 61, and 85 % were women. Feasibility criteria were met. Fasting-related toxicities were limited to ≤ grade 2, most commonly fatigue, headache, and dizziness. The COMET assay indicated reduced DNA damage in leukocytes from subjects who fasted for ≥48 h (p = 0.08). There was a non-significant trend toward less grade 3 or 4 neutropenia in the 48 and 72 h cohorts compared to 24 h cohort (p = 0.17). IGF-1 levels decreased by 30, 33 and 8 % in the 24, 48 and 72 h fasting cohorts respectively after the first fasting period. Fasting for 72 h around chemotherapy administration is safe and feasible for cancer patients. Biomarkers such as IGF-1 may facilitate assessment of differences in chemotherapy toxicity in subgroups achieving the physiologic fasting state. An onging randomized trial is studying the effect of 72 h of fasting. Clinicaltrials.gov: NCT00936364, registered propectively on July 9, 2009. The online version of this article (doi:10.1186/s12885-016-2370-6) contains supplementary material, which is available to authorized users

Doxorubicin Loaded Chitosan-W18 O49 Hybrid Nanoparticles for Combined Photothermal-Chemotherapy.

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Yuan, Shanmei; Hua, Jisong; Zhou, Yinyin; Ding, Yin; Hu, Yong

2017-08-01

Combined treatment is more effective than single treatment against most forms of cancer. In this work, doxorubicin loaded chitosan-W 18 O 49 nanoparticles combined with the photothermal therapy and chemotherapy are fabricated through the electrostatic interaction between positively charged chitosan and negatively charged W 18 O 49 nanoparticles. The in vitro and in vivo behaviors of these nanoparticles are examined by dynamic light scattering, transmission electron microscopy, cytotoxicity, near-infrared fluorescence imaging, and tumor growth inhibition experiment. These nanoparticles have a mean size around 110 nm and show a pH sensitive drug release behavior. After irradiation by the 980 nm laser, these nanoparticles show more pronounced cytotoxicity against HeLa cells than that of free doxorubicin or photothermal therapy alone. The in vivo experiments confirm that their antitumor ability is significantly improved, resulting in superior efficiency in impeding tumor growth and extension of the lifetime of mice. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Radical resection for low rectal carcinoma combined with infusion pump chemotherapy via internal iliac artery

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Bo YANG

2011-10-01

Full Text Available Objective To evaluate the effects and practicability of radical resection for low rectal carcinoma with infusion pump chemotherapy via internal iliac artery,and explore the correlation factors influencing the therapeutic effects.Methods Data of 316 patients with low rectal carcinoma,admitted from Oct.1997 to Mar.2008,were retrospectively analyzed and assigned into 2 groups according to the treatment: Patients received infusion pump chemotherapy via internal iliac artery to target area combined with intravenous systemic chemotherapy were assigned into group A(n=249,and those receiving systemic chemotherapy alone following radical resection were assigned to group B(n=67.The timing of pump chemotherapy to target area in group A was set at day 12 after recovery of digestive function,with regimen of 5-FU at 0.5g per dose plus hydroxycamptothecin at 10-15mg per dose,twice a week,four times as a treatment course for a total of 6 courses,and it was followed by intravenously systemic chemotherapy with a regimen of FOLFIRI or FOLFOX.In group B,at day 12 right after recovery of digestive function,the intravenous sytemic chemotherapy was started with the same regimen as in group A.The local recurrence rate,metastasis rate and survival rate after 1,3 and 5 years in the two groups were respectively observed and compared,and the correlation between the clinicopathological features and the 5 year local recurrence rates and survival rates was analyzed in patients of group A.Results In group A,the local recurrence rate at year 1,3 and 5 was 0,1.68%(4/238 and 3.79%(8/211,respectively,the metastasis rate was 0.80%(2/249,4.62%(11/238 and 10.90%(23/211,respectively,and the survival rate was 100%,77.73%(185/238 and 72.04%(152/211,respectively.In group B,the local recurrence rate at year 1,3 and 5 was 0,9.52%(6/63 and 16.36%(9/55,respectively,the metastasis rate was 1.49%(1/67,15.87%(10/63 and 27.27%(15/55,respectively,and the survival rate was 100

Efficacy and Safety of Rituximab in the Treatment of Vasculitic Leg Ulcers Associated with Hepatitis C Virus Infection

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Fabio Bonilla-Abadía

2012-01-01

Full Text Available Vasculitic leg ulcers are a cutaneous manifestation of hepatitis C virus (HCV infection often associated with cryoglobulinemia. Their treatment is difficult and is based on steroids and immunosuppressive drugs with an erratic response and a high probability of adverse reaction. We report three patients with vasculitic leg ulcers associated with hepatitis C virus infection who were treated successfully with rituximab. The pain control and healing were achieved quickly. No adverse effects with rituximab in these patients were presented.

Efficacy of intensity-modulated radiotherapy combined with chemotherapy or surgery in locally advanced squamous cell carcinoma of the head-and-neck

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Yang H

2013-10-01

Full Text Available Hua Yang,* Li-Qiong Diao,* Mei Shi, Rui Ma, Jian-Hua Wang, Jian-Ping Li, Feng Xiao, Ying Xue, Man Xu, Bin ZhouDepartment of Radiotherapy Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China*These authors contributed equally to this workObjectives: Long-term locoregional control following intensity-modulated radiotherapy (IMRT for locally advanced squamous cell carcinoma of the head-and-neck (SCCHN remains challenging. This study aimed to assess the efficacy and toxicity of IMRT with and without chemotherapy or surgery in locally advanced SCCHN.Materials and methods: Between January 2007 and January 2011, 61 patients with locally advanced SCCHN were treated with curative IMRT in the Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University; 28% underwent definitive IMRT and 72% postoperative IMRT, combined with simultaneous cisplatin-based chemotherapy in 58%. The mean doses of definitive and postoperative IMRT were 70.8 Gy (range, 66–74 Gy. Outcomes were analyzed using Kaplan–Meier curves. Acute and late toxicities were graded according to Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer radiation morbidity scoring criteria.Results: At a median follow-up of 35 months, 3-year local recurrence-free survival (LRFS, regional recurrence-free survival (RRFS, distant metastasis-free survival (DMFS, disease-free survival (DFS, and overall survival (OS were 83.8%, 86.1%, 82.4%, 53.2%, and 62%, respectively. Postoperative IMRT (n = 44, 72% had significantly higher LRFS/OS/DMFS than definitive IMRT (n = 17, 28%; P < 0.05. IMRT combined with chemotherapy (n = 35, 58% had significantly higher LRFS/OS/DMFS than IMRT alone (n = 26, 42%; P < 0.05. One year after radiotherapy, the incidence of xerostomia of grade 1, 2, or 3 was 13.1%, 19.7%, and 1.6%, respectively. No grade 4 acute or late toxicity was observed.Conclusion: IMRT combined with

Efficacy of rituximab and plasmapharesis in an adult patient with antifactor H autoantibody-associated hemolytic uremic syndrome: A case report and literature review.

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Deville, Clemence; Garrouste, Cyril; Coppo, Paul; Evrard, Bertrand; Lautrette, Alexandre; Heng, Anne Elisabeth

2016-09-01

Antifactor H antibody (anti-CFHAb) is found in 6% to 25% cases of atypical hemolytic uremic syndrome (aHUS) in children, but has been only exceptionally reported in adults. There is no consensus about the best treatment for this type of aHUS. We report the case of an adult patient treated successfully with plasma exchange (PE), steroids, and rituximab.A 27-year-old Caucasian male presented to hospital with anemia, thrombocytopenia, and acute renal failure. One week earlier, he had digestive problems with diarrhea. The diagnosis of anti-CFHAb-associated aHUS (82,000 AU/mL) without CFHR gene mutations was established.He received Rituximab 375 mg/m (4 pulses) with PE and steroids. This treatment achieved renal and hematological remission at day (D) 31 and negative anti-CFHAb at D45 (<100 AU/mL). At D76, a fifth rituximab pulse was performed while CD19 was higher than 10/mm. Steroids were stopped at month (M) 9. The patient has not relapsed during long-term follow-up (M39).Rituximab therapy can be considered for anti-CFHAb-associated aHUS. Monitoring of anti-CFHAb titer may help to guide maintenance therapeutic strategies including Rituximab infusion.

Internalization of rituximab and the efficiency of B Cell depletion in rheumatoid arthritis and systemic lupus erythematosus.

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Reddy, Venkat; Cambridge, Geraldine; Isenberg, David A; Glennie, Martin J; Cragg, Mark S; Leandro, Maria

2015-05-01

Rituximab, a type I anti-CD20 monoclonal antibody (mAb), induces incomplete B cell depletion in some patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), thus contributing to a poor clinical response. The mechanisms of this resistance remain elusive. The purpose of this study was to determine whether type II mAb are more efficient than type I mAb at depleting B cells from RA and SLE patients, whether internalization influences the efficiency of depletion, and whether Fcγ receptor type IIb (FcγRIIb) and the B cell receptor regulate this internalization process. We used an in vitro whole blood B cell-depletion assay to assess the efficiency of depletion, flow cytometry to study cell surface protein expression, and surface fluorescence-quenching assays to assess rituximab internalization, in samples from patients with RA and patients with SLE. Paired t-test or Mann-Whitney U test was used to compare groups, and Spearman's rank correlation test was used to assess correlation. We found that type II mAb internalized significantly less rituximab than type I mAb and depleted B cells from patients with RA and SLE at least 2-fold more efficiently than type I mAb. Internalization of rituximab was highly variable between patients, was regulated by FcγRIIb, and inversely correlated with cytotoxicity in whole blood B cell-depletion assays. The lowest levels of internalization were seen in IgD- B cells, including postswitched (IgD-CD27+) memory cells. Internalization of type I anti-CD20 mAb was also partially inhibited by anti-IgM stimulation. Variability in internalization of rituximab was observed and was correlated with impaired B cell depletion. Therefore, slower-internalizing type II mAb should be considered as alternative B cell-depleting agents for the treatment of RA and SLE. © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

[Efficacy and safety of rituximab in the treatment of primary antiphospholipid syndrome: analysis of 24 cases from the bibliography review].

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Pons, Isaac; Espinosa, Gerard; Cervera, Ricard

2015-02-02

Antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (aPL) and thrombotic and/or obstetric manifestations. Patients without another associated autoimmune disease are considered to have primary APS. Some patients develop thrombosis recurrence despite anticoagulant treatment and some clinical features do not respond to standard therapy. Rituximab may be an alternative in these cases. We review the published scientific evidence on the use of rituximab in the treatment of primary APS. Description of a case and review of the literature with descriptive analysis of the demographic, clinical, and immunologic features, treatment and outcome of patients. We identified 24 patients (15 women [62.5%]), with a mean age of 37.0 ± 13.4 years. The reasons for the use of rituximab were thrombocytopenia (41.7%), skin involvement (33.3%), neurologic and heart valve involvement (12.5%), hemolytic anemia (8.3%) and pulmonary and renal involvement (4.2%). Lupus anticoagulant was present in 72.7% of the cases, the IgG and IgM isotypes of anticardiolipin antibodies in 75 and 50%, respectively, and the anti-β2GPI (IgG e IgM) antibodies in 80% of patients. Thirteen (54.1%) patients received 2 doses of 1,000 mg of rituximab fortnightly, 10 (41.7%) 4 doses of 375 mg/m(2) weekly and one (4.2%) 8 doses of 375 mg/m(2) weekly. Eleven (45.8%) patients presented a complete clinical response, 7 (29.2%) a partial response and 6 (25%) did not respond to rituximab. Four patients with clinical improvement presented with aPL titer decrease and in one patient, aPL levels did not change. In one patient without clinical response, aPL remained positive. A clinical-immunologic dissociation existed in 2 additional cases. The results obtained suggest a possible potential benefit of rituximab in the treatment of some clinical manifestations of primary APS such as thrombocytopenia, skin and heart valve involvement. Copyright © 2013 Elsevier España, S.L.U. All rights

Utilization of special computerized tomography and nuclear medicine techniques for quality control and for the optimization of combined precision chemotherapy and precision radiation therapy

International Nuclear Information System (INIS)

Wiley, A.L. Jr.; Wirtanen, G.W.; Chien, I.-C.

1984-01-01

A combination of precision (selective, intra-arterial) chemotherapy and precision radiotherapy can be used for advanced pancreatic, biliary tract, and sarcomatous malignancies. There were some remarkable responses, but also a few poor responses and even some morbidity. Accordingly, methods are developed of pre-selecting those patients whose tumors are likely to respond to such therapy, as well as methods for improving the therapeutic ratio by the rational optimization of combined therapy. Specifically, clinical tumor blood flow characteristics (monitored with nuclear medicine techniques) may provide useful criteria for such selection. The authors also evaluate qualitatively the drug distribution or exposure space with specialized color-coded computerized tomography images, which demonstrate spatially dependent enhancement of intra-arterial contrast in tumor and in adjacent normal tissues. Such clinical data can improve the quality control aspects of intra-arterial chemotherapy administration, as well as the possibility of achievement of a significant therapeutic ratio by the integration of precision chemotherapy and precision radiation therapy. (Auth.)

First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10)

DEFF Research Database (Denmark)

Eichhorst, Barbara; Fink, Anna-Maria; Bahlo, Jasmin

2016-01-01

BACKGROUND: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less....... The final analysis was done by intention to treat. The study is registered with ClinicalTrials.gov, number NCT%2000769522. FINDINGS: 688 patients were recruited between Oct 2, 2008, and July 11, 2011, of which 564 patients who met inclusion criteria were randomly assigned. 561 patients were included...

Refractory myasthenia gravis – clinical profile, comorbidities and response to rituximab

Science.gov (United States)

Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

2016-01-01

Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27–53 years. In our study 25 patients (32.89%) belonged to the age group of 21–30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% (p=3.3x10–8) to 94.6% (p=2.2x10–14) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low. PMID:27790079

[A case report-advanced pancreas cancer with liver and lung metastases well controlled over one year by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion in an outpatient setting].

Science.gov (United States)

Hasuike, Yasunori; Tanigawa, Takahiko; Yamada, Masaharu; Minami, Yukiko; Ezumi, Koji; Kashiwazaki, Masaki; Fujimoto, Takayoshi

2008-11-01

We report a case of advanced pancreatic cancer with liver and lung metastases that was well controlled over one year by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion in an outpatient setting. The patient was a 74-year-old woman. Chief complaints were back pain and anorexia. She was diagnosed with pancreas cancer with liver and lung metastases at the time of first visit. We started systemic chemotherapy with gemcitabine 1 g/body and 5-FU 1 g/body alternately every other week on an outpatient basis. At 1.5 months (M) after initiation of chemotherapy, we started radiation therapy to the main tumor at a total dose of 40 Gy. After radiation, chemotherapy was resumed. As a result, the size of the main tumor decreased but metastatic liver tumors got larger. Then we changed to combination therapy with systemic chemotherapy (gemcitabine and 5-FU) and hepatic arterial infusion (5-FU weekly). Liver metastases almost disappeared after 7.5 M. Despite all these treatments, however, the number of metastatic lung tumors increased. The patient was hospitalized for 15 M and died after 17 M. We focused on and succeeded in the prolongation of lifetime and maintenance of QOL by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion therapy.

Comparison between Antiemetic Effects of Palonosetron and Granisetron on Chemotherapy-Induced Nausea and Vomiting in Japanese Patients Treated with R-CHOP.

Science.gov (United States)

Uchida, Mayako; Mori, Yasuo; Nakamura, Tsutomu; Kato, Koji; Kamezaki, Kenjiro; Takenaka, Katsuto; Shiratsuchi, Motoaki; Kadoyama, Kaori; Miyamoto, Toshihiro; Akashi, Koichi